Gene Summary

Gene:BIRC5; baculoviral IAP repeat containing 5
Aliases: API4, EPR-1
Summary:This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:baculoviral IAP repeat-containing protein 5
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 30 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (9)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Breast CancerBIRC5 and Breast Cancer View Publications375
Lung Cancer, Small CellSurvivin Expression in Colorectal Cancer View Publications315
Lung CancerSurvivin Expression in Non Small Lung Cancer
Researchers in Germany (Monzo, 1999) used RT-PCR to detect survivin gene transcripts in 83 NSCLC tumour samples and in paired normal lung tissues. The survivin gene transcript was found in 71 (86%) of the tumours and in only 10 (12%) of the normal lung samples. Moreover, the 12 patients without survivin expression were found to have significantly better survival than the 71 patients with survivin expression.
View Publications170
Bladder CancerBIRC5 and Bladder Cancer View Publications163
Skin CancerBIRC5 and Skin Cancer View Publications91
NeuroblastomaSurvivin Expression in Neuroblastoma View Publications69
Thyroid CancerBIRC5 and Thyroid Cancer View Publications33
Wilms TumourBIRC5 and Wilms Tumour View Publications6

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: BIRC5 (cancer-related)

Namgung Y, Kim SY, Kim I
Down-regulation of Survivin by BIX-01294 Pretreatment Overcomes Resistance of Hepatocellular Carcinoma Cells to TRAIL.
Anticancer Res. 2019; 39(7):3571-3578 [PubMed] Related Publications
BACKGROUND/AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cancer-selective, cell-death-inducing agent with little toxicity to normal cells. However, various human cancers and cancer cell lines have been reported to be resistant to TRAIL. Molecular clarification of resistance mechanism is needed.
MATERIALS AND METHODS: Compound screening, proliferation assays, western blotting, and flow cytometry were used to examine the sensitizer activity of methyl transferase inhibitor BIX-01294 in combination with TRAIL, in hepatocellular carcinoma (HCC) cells. RNA sequencing analysis and single guide (sg)RNA-mediated gene deletion were used to investigate the role of survivin in sensitization.
RESULTS: In HCC cells, BIX-01294 enhanced TRAIL sensitivity by reducing survivin expression at the RNA level. Small interference RNA-mediated gene knockdown demonstrated the mechanism of sensitization to be via the reduction of survivin.
CONCLUSION: Euchromatin histone methyltransferase 2 (EHMT2) inhibition by BIX-01294 may be a potent anti-tumor therapeutic strategy for human HCC.

Cao Y, Zhu W, Chen W, et al.
Prognostic Value of BIRC5 in Lung Adenocarcinoma Lacking EGFR, KRAS, and ALK Mutations by Integrated Bioinformatics Analysis.
Dis Markers. 2019; 2019:5451290 [PubMed] Free Access to Full Article Related Publications
Objective: This study was aimed at investigating the prognostic significance of Baculoviral IAP repeat containing 5 (BIRC5) in lung adenocarcinoma (LAD) lacking EGFR, KRAS, and ALK mutations (triple-negative (TN) adenocarcinomas).
Methods: The gene expression profiles were obtained from Gene Expression Omnibus (GEO). The identification of the differentially expressed genes (DEGs) was performed by GeneSpring GX. Gene set enrichment analysis (GSEA) was used to execute gene ontology function and pathway enrichment analysis. The protein interaction network was constructed by Cytoscape. The hub genes were extracted by MCODE and cytoHubba plugin from the network. Then, using BIRC5 as a candidate, the prognostic value in LAD and TN adenocarcinomas was verified by the Kaplan-Meier plotter and The Cancer Genome Atlas (TCGA) database, respectively. Finally, the mechanism of BIRC5 was predicted by a coexpressed network and enrichment analysis.
Results: A total of 38 upregulated genes and 121 downregulated genes were identified. 9 hub genes were extracted. Among them, the mRNA expression of 5 genes, namely, BIRC5, MCM4, CDC20, KIAA0101, and TRIP13, were significantly upregulated among TN adenocarcinomas (all
Conclusion: Overexpressed in tumors, BIRC5 is associated with unfavorable overall survival in TN adenocarcinomas. BIRC5 is a potential predictor and therapeutic target in TN adenocarcinomas.

Patil S, Sankpal UT, Hurtado M, et al.
Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells.
Gene. 2019; 705:67-76 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Medulloblastoma (MB) is characterized by highly invasive embryonal neuro-epithelial tumors that metastasize via cerebrospinal fluid. MB is difficult to treat and the chemotherapy is associated with significant toxicities and potential long-term disabilities. Previously, we showed that small molecule, clotam (tolfenamic acid: TA) inhibited MB cell proliferation and tumor growth in mice by targeting, survivin. Overexpression of survivin is associated with aggressiveness and poor prognosis in several cancers, including MB. The aim of this study was to test combination treatment involving Vincristine® (VCR), a standard chemotherapeutic drug for MB and TA against MB cells. DAOY and D283 MB cells were treated with 10 μg/mL TA or VCR (DAOY: 2 ng/mL; D283: 1 ng/mL) or combination (TA + VCR). These optimized doses were lower than individual IC

Özdemir MD, Göktürk D
The concurrent effect of acyclovir and rosemary on glioblastoma cell culture.
Cell Mol Biol (Noisy-le-grand). 2019; 65(3):66-71 [PubMed] Related Publications
Human cytomegalovirus (HCMV) is a beta herpesvirus which large amount of people in world has interacted with. Recent studies indicated that CMV DNA is associated with several cancer types including "Glioblastoma (GBM)" which is the most common and aggressive type of primary brain cancer. In clinical studies it was shown that several antiviral medicines prolonged life span of glioblastoma patients. One of them is Acyclovir (ACV) which is a type of nucleoside analog, used to cure viral infections and might be a potential treatment supplement for Glioblastoma. In this study we aimed to investigate if ACV had cytotoxic effect on glioblastoma cell line U87 MG and also the effect of ACV on healthy cells. Furthermore it was aimed to search the effect of Rosmarinus Officinalis also known as rosemary which is an aromatic, perennial plant concurrent with ACV on glioblastoma and healthy cells.

Huang J, Wei Y, Zhou X, et al.
The association between survivin -31G>C polymorphism and susceptibility to sporadic colorectal cancer in a Southern Chinese population.
J Cancer Res Ther. 2019 Jan-Mar; 15(1):82-86 [PubMed] Related Publications
Background: The case-control study aimed to investigate the association between the -31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population.
Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene -31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and -31G>C genetic polymorphism was estimated using an unconditional logistic regression model.
Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and -31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin -31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m
Conclusion: Survivin -31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The -31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m

Xiong H, Cheng J, Jiang S, et al.
The antitumor effect of resveratrol on nasopharyngeal carcinoma cells.
Front Biosci (Landmark Ed). 2019; 24:961-970 [PubMed] Related Publications
The anti-tumor effect of resveratrol has been observed in many cancers. Here, we examined the anti-tumor activity of resveratrol in human nasopharyngeal carcinoma (NPC) cells. Resveratrol, in a dose-dependent manner, inhibited proliferation related proteins (Ki67, PCNA), and cell proliferation, and reduced apoptosis related proteins (cleaved caspase-3, cleaved caspase-9) and apoptosis in nasopharyngeal carcinoma cells. Resveratrol treatment inhibited the increased-expression of Survivin in NPC cells, while the overexpressed Survivin counteracted the effect of resveratrol on cell proliferation and apoptosis in NPC cells, thus establishing Resveratrol-induced reduction in increased-survivin in NPC cells as the underlying mechanism. These findings show that resveratrol can be used to modify the cell growth and death in NPC cells.

Lee MJ, Tsai YJ, Lin MY, et al.
Calebin-A induced death of malignant peripheral nerve sheath tumor cells by activation of histone acetyltransferase.
Phytomedicine. 2019; 57:377-384 [PubMed] Related Publications
BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. The malignant peripheral nerve sheath tumor (MPNST), transformed from NF1 related plexiform neurofibroma, is a rapidly growing and highly invasive tumor. No effective chemotherapeutic agent is currently available. Calebin-A is a derivative from turmeric Curcuma longa. Given the anti-inflammatory and anticancer potentials of curcumin, whether Calebin-A also had the tumoricidal effect upon MPNST cells is still elusive.
PURPOSE: To determine whether Calebin-A has the potential for anti-MPNST effect.
METHODS: The MTT and FACS analysis of normal Schwann (HSC) and MPNST cells have been employed to determine the tumoricidal effect of Calebin-A. The expression of the signal pathway molecules was assessed by Western blotting. The CHIP with quantitative PCR assay was performed to quantify the promoter DNA binding to acetylated histone 3 (acetyl H3). The enzyme activities of histone acetyltransferase (HAT) and deacetylase (HDAC) have been evaluated by commercial kits. The measurements of tumor size of the xenograft mouse model were also performed.
RESULTS: Calebin-A inhibited the proliferation of MPNST and primary neurofibroma cells in a dose-dependent manner. The flow cytometry analysis of the MPNST cells after treatment of 25 μm of Calebin-A demonstrated an increase of population in the G0/G1 phase but decrease in G2/M phase. Before treatment, the expression of Axl, Tyro3, and acetyl H3 was significantly higher in MPNST cells when compared to HSC. The expression of phosphorylated-AKT, -ERK1/2, survivin, hTERT, and acetyl H3 proteins were reduced after treatment. The CHIP assay shows the promoter DNA copies of survivin (BRIC5) and hTERT genes are significantly reduced post-treatment. The enzyme activity of HAT was significantly reduced, but not that of HDAC. Two HAT inhibitors, epigallocatechin-3-gallate (EGCG) and anacardic acid (AA) have also demonstrated a significant inhibitory effect on MPNST cells. Finally, the measurements of tumor size showed a significant reduction of the xenograft tumors after treatment of Calebin-A.
CONCLUSION: Both in vitro and in vivo studies showed Calebin-A could inhibit the proliferation of MPNST with suppression of survivin and hTERT. The reduced expression of these two factors might be through the epigenetic histone modification resulting from the decreased activity of HAT.

Braný D, Dvorská D, Kúdela E, et al.
Potential of survivin for treatment of gynaecological tumour diseases.
Ceska Gynekol. Winter 2018; 83(3):226-231 [PubMed] Related Publications
OBJECTIVE: The main purpose of this article is to consolidate known facts about survivin, its contribution to inhibition of apoptosis, impact to tumorigenesis of gynaecological types of tumours. and possibilities of inhibition of survivin on molecular-genetic levels.
DESIGN: A review article.
SETTINGS: Division of Molecular Medicine, Biomedical Center in Martin, JLF UK Martin, Slovakia; Department of Gynaecology and Obstetrics JLF UK and UNM Martin, Slovakia; Division of Oncology, Biomedical Center, JLF UK Martin, Slovakia.
METHODS: An analysis of the literature using database search engines focused on aberations in fuction of survivin, primarily in case of gynaecological tumours and possibilities of its inhibition.
RESULTS AND CONCLUSIONS: Survivin is the smallest member of inhibitor of apoptosis (IAP) family. Despite of its size and affiliation to mentioned gene family, survivin can affect besides inhibition of apoptosis also proper process of mitosis, DNA reparation and angiogenesis. High levels of survivin expression are typical for fetal tissues during intrauterine developement. In healthy, adult tissues remain levels of survivin very low. Nonetheless, abundant expression of survivin is in many cases typical for various types of cancer, including gynaecologycal cancers Generally, it is possible to associate higher amounts of survivin with poor prognosis and resistance to chemo- or radiotherapy.

Moazeni-Roodi A, Ghavami S, Hashemi M
Survivin rs9904341 polymorphism significantly increased the risk of cancer: evidence from an updated meta-analysis of case-control studies.
Int J Clin Oncol. 2019; 24(4):335-349 [PubMed] Related Publications
AIMS: Survivin, a member of inhibitor of apoptosis protein family, is involved in the regulation of cell cycle and apoptosis. Several studies inspected the association between survivin polymorphisms and the risk of various cancers, but the findings remain controversial. We conducted a meta-analysis intending to certify the association between survivin polymorphisms and cancer risk.
METHODS: All analyses were achieved using RevMan 5.3 software and STATA 14.1 software. Eligible studies were collected by comprehensive literature searching Web of Science, PubMed, Scopus, and Google scholar databases. Pooled estimates of odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the overall impact of survivin polymorphisms on cancer risk.
RESULTS: The overall analysis indicates that survivin rs9904341 polymorphism significantly increased the risk of cancer in homozygous codominant (OR 1.41, 95% CI 1.19-1.68, p = 0.0001, CC vs GG), dominant (OR 1.22, 95% CI 1.07-1.40, p = 0.003, CG+CC vs GG), recessive (OR 1.34, 95% CI 1.18-1.52, p < 0.0001, CC vs CG+GG), and allele (OR 1.20, 95% CI 1.09-1.31, p = 0.0001, C vs G) inheritance models tested. Stratified based on ethnicity revealed that rs9904341 variant significantly increased the risk of cancer in the Asian population. The findings did not support an association between rs1042489, rs2071214, rs8073069, and rs17878467 polymorphisms and risk of cancer.
CONCLUSIONS: The current study suggests that the survivin rs9904341 polymorphism may be associated with the risk of cancer either overall or in the Asian population. However, further larger and well-designed studies are warranted to evaluate this association in detail.

Yamamoto M, Suzuki S, Togashi K, et al.
AS602801 Sensitizes Ovarian Cancer Stem Cells to Paclitaxel by Down-regulating MDR1.
Anticancer Res. 2019; 39(2):609-617 [PubMed] Related Publications
BACKGROUND/AIM: AS602801, an anti-cancer stem cell (CSC) candidate drug, sensitizes ovarian CSCs to paclitaxel and carboplatin by reducing the expression of survivin, an anti-apoptotic protein. The aim of the study was to examine the effect of AS602801 on the expression of multi drug resistance protein 1 (MDR1).
MATERIALS AND METHODS: Using two ovarian CSC lines, A2780 CSLC and TOV-21G CSLC, mechanisms other than survivin down-regulation were examined by comparing the effects of AS602801 and YM155, an inhibitor of survivin. After screening for the expression of ATP-binding cassette (ABC) transporters with or without AS602801 treatment, the sensitivity of cells to paclitaxel, carboplatin, and cisplatin was examined following knockdown of the ABC transporter.
RESULTS: The combinational effect of AS602801 on paclitaxel was less dependent on survivin than the effect on carboplatin. AS602801 reduced the expression of MDR1, an ABC transporter. Knockdown of MDR1 sensitized the cells to paclitaxel, but not to carboplatin or cisplatin.
CONCLUSION: AS602801 chemosensitized ovarian CSCs to paclitaxel by reducing the expression of MDR1.

Mahmoudian-Sani MR, Alghasi A, Saeedi-Boroujeni A, et al.
Survivin as a diagnostic and therapeutic marker for thyroid cancer.
Pathol Res Pract. 2019; 215(4):619-625 [PubMed] Related Publications
Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.

Oh HN, Oh KB, Lee MH, et al.
JAK2 regulation by licochalcone H inhibits the cell growth and induces apoptosis in oral squamous cell carcinoma.
Phytomedicine. 2019; 52:60-69 [PubMed] Related Publications
BACKGROUND: Licochalconce (LC) H is an artificial compound in the course of synthesizing LCC in 2013. So far, few studies on the effects of LCH have been found in the literature. Despite progress in treatment modalities for oral cancer, the cure from cancer has still limitations.
PURPOSE: The effects of LCH were investigated on human oral squamous cell carcinoma (OSCC) cells to elucidate its mechanisms.
STUDY DESIGN: We explored the mechanism of action of LCH by which it could have effects on JAK2/STAT3 signaling pathway.
METHODS: To confirm LCH anti-cancer effect, analyzed were MTT assay, DAPI staining, soft agar, kinase assay, molecular docking simulation, flow cytometry and Western blotting analysis.
RESULTS: According to docking and molecular dynamics simulations, the predicted pose of the complex LCH and JAK2 seems reasonable and LCH is strongly bound to active JAK2 with opened activation loop. The LCH inhibitor is surrounded by specific ATP-binding pocket in which it is stabilized by forming hydrogen bonds and hydrophobic interactions. It is shown that LCH plays as a competitive inhibitor in an active state of JAK2. LCH caused a dose-dependent decrease in phosphorylation of JAK2 and STAT3. More interestingly, LCH suppressed JAK2 kinase activity in vitro by its direct binding to the JAK2. LCH significantly inhibited the JAK2/STAT3 signaling pathway, causing the down-regulation of target genes such as Bcl-2, survivin, cyclin D1, p21 and p27. In addition, LCH inhibited cell proliferation and colony formation of OSCC cells in a dose- and time-dependent manner, as well as induction of cell apoptosis through extrinsic and intrinsic pathway. The induction of apoptosis in OSCC cells by LCH was evident in the increased production of ROS, loss of mitochondrial membrane potential, release of cyto c, variation of apoptotic proteins and activation of caspase cascade.
CONCLUSION: LCH not only induces apoptosis in OSCC cells through the JAK/STAT3 signaling pathway but also inhibits cell growth. It is proposed that LCH has a promising use for the chemotherapeutic agent of oral cancer.

Lee MG, Lee KS, Nam KS
The association of changes in RAD51 and survivin expression levels with the proton beam sensitivity of Capan‑1 and Panc‑1 human pancreatic cancer cells.
Int J Oncol. 2019; 54(2):744-752 [PubMed] Related Publications
Fewer than 20% of patients diagnosed with pancreatic cancer can be treated with surgical resection. The effects of proton beam irradiation were evaluated on the cell viabilities in Panc‑1 and Capan‑1 pancreatic cancer cells. The cells were irradiated with proton beams at the center of Bragg peaks with a 6‑cm width using a proton accelerator. Cell proliferation was assessed with the MTT assay, gene expression was analyzed with semi‑quantitative or quantitative reverse transcription‑polymerase chain reaction analyses and protein expression was evaluated by western blotting. The results demonstrated that Capan‑1 cells had lower cell viability than Panc‑1 cells at 72 h after proton beam irradiation. Furthermore, the cleaved poly (ADP‑ribose) polymerase protein level was increased by irradiation in Capan‑1 cells, but not in Panc‑1 cells. Additionally, it was determined that histone H2AX phosphorylation in the two cell lines was increased by irradiation. Although a 16 Gy proton beam was only slightly up‑regulated cyclin‑dependent kinase inhibitor 1 (p21) protein expression in Capan‑1 cells, p21 expression levels in Capan‑1 and Panc‑1 cells were significantly increased at 72 h after irradiation. Furthermore, it was observed that the expression of DNA repair protein RAD51 homolog 1 (RAD51), a homogenous repair enzyme, was decreased in what appeared to be a dose‑dependent manner by irradiation in Capan‑1 cells. Contrastingly, the transcription of survivin in Panc‑1 was significantly enhanced. The results suggest that RAD51 and survivin are potent markers that determine the therapeutic efficacy of proton beam therapy in patients with pancreatic cancer.

Urtishak KA, Wang LS, Culjkovic-Kraljacic B, et al.
Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia.
Oncogene. 2019; 38(13):2241-2262 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
The poor outcomes in infant acute lymphoblastic leukemia (ALL) necessitate new treatments. Here we discover that EIF4E protein is elevated in most cases of infant ALL and test EIF4E targeting by the repurposed antiviral agent ribavirin, which has anticancer properties through EIF4E inhibition, as a potential treatment. We find that ribavirin treatment of actively dividing infant ALL cells on bone marrow stromal cells (BMSCs) at clinically achievable concentrations causes robust proliferation inhibition in proportion with EIF4E expression. Further, we find that ribavirin treatment of KMT2A-rearranged (KMT2A-R) infant ALL cells and the KMT2A-AFF1 cell line RS4:11 inhibits EIF4E, leading to decreases in oncogenic EIF4E-regulated cell growth and survival proteins. In ribavirin-sensitive KMT2A-R infant ALL cells and RS4:11 cells, EIF4E-regulated proteins with reduced levels of expression following ribavirin treatment include MYC, MCL1, NBN, BCL2 and BIRC5. Ribavirin-treated RS4:11 cells exhibit impaired EIF4E-dependent nuclear to cytoplasmic export and/or translation of the corresponding mRNAs, as well as reduced phosphorylation of the p-AKT1, p-EIF4EBP1, p-RPS6 and p-EIF4E signaling proteins. This leads to an S-phase cell cycle arrest in RS4:11 cells corresponding to the decreased proliferation. Ribavirin causes nuclear EIF4E to re-localize to the cytoplasm in KMT2A-AFF1 infant ALL and RS4:11 cells, providing further evidence for EIF4E inhibition. Ribavirin slows increases in peripheral blasts in KMT2A-R infant ALL xenograft-bearing mice. Ribavirin cooperates with chemotherapy, particularly L-asparaginase, in reducing live KMT2A-AFF1 infant ALL cells in BMSC co-cultures. This work establishes that EIF4E is broadly elevated across infant ALL and that clinically relevant ribavirin exposures have preclinical activity and effectively inhibit EIF4E in KMT2A-R cases, suggesting promise in EIF4E targeting using ribavirin as a means of treatment.

Mazoochi T, Karimian M, Ehteram H, Karimian A
Survivin c.-31G>C (rs9904341) gene transversion and urinary system cancers risk: a systematic review and a meta-analysis.
Per Med. 2019; 16(1):67-78 [PubMed] Related Publications
AIM: To investigate the possible association between survivin c.-31G>C (rs9904341) gene polymorphism and urinary system cancers by a meta-analysis approach.
METHODS: Standard electronic literature databases were searched to find eligible studies. The odds ratios (ORs) with 95% CIs were estimated to find the associations possibility.
RESULTS: Overall meta-analysis revealed significant associations between c.-31G>C transversion and risk of urinary tract cancers in dominant (OR: 1.34; 95% CI: 1.02-1.75; p = 0.035), recessive (OR: 1.52; 95% CI: 1.33-1.74; p < 0.001) and homozygote codominant (OR: 1.90; 95% Cl: 1.37-2.62; p < 0.001) genetic models.
CONCLUSION: The c.-31G>C transversion might be a risk factor for urinary system cancers. However, more articles with different ethnicities will help to obtain a more accurate conclusion.

Mokhtary P, Javan B, Sharbatkhari M, et al.
Cationic vesicles for efficient shRNA transfection in the MCF-7 breast cancer cell line.
Int J Nanomedicine. 2018; 13:7107-7121 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Introduction: Novel and safe delivery solutions for RNAi therapeutics are essential to obtain the full potential of cancer gene therapy.
Methods: In this study, cationic vesicular nanocarrier was applied for delivering lnc urothelial carcinoma-associated 1 (lnc UCA1) shRNA expression vector to MCF-7 cells. The physicochemical characteristics, cytotoxicity, and transfection efficiency of cationic vesicles prepared from various molar ratios of amphiphilic surfactant Tween 80 (T), squalene (S), cationic charge lipid didodecyldimethylammonium bromide, and polyethylenimine were investigated. The particle sizes of the vesicles in the nanosize range were determined by dynamic light scattering and transmission electron microscopy.
Results: Gel protection assay with agarose gel electrophoresis showed cationic vesicles can protect the shRNA plasmid from DNase 1 enzyme. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt result showed no significant cytotoxicity was caused in MCF-7 cancer cell line by (T:S):polyethylenimine cationic vesicles. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, fluorescence microscope images, and flow cytometry analyses confirmed that (T:S)
Conclusion: The novel nonviral vesicular nanocarrier, (T:S)

Dittharot K, Dakeng S, Suebsakwong P, et al.
Cucurbitacin B Induces Hypermethylation of Oncogenes in Breast Cancer Cells.
Planta Med. 2019; 85(5):370-378 [PubMed] Related Publications
Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes including aberrant promoter methylation plays a critical role in human breast carcinogenesis. Cucurbitacin B has antiproliferative activity against various human breast cancer cells, but the molecular mechanism is not completely understood. In this study, we explore the influence of cucurbitacin B from

Budak M, Bozkurt C, Cetin SE, Tuncel H
The -31 G/C promoter gene polymorphism of surviving in Turkish colorectal cancers patients
Ceylon Med J. 2018; 63(3):119-123 [PubMed] Related Publications
Introduction: Survivin (also known as birc5) is the first protein discovered among the apoptosis-regulating gene family referred to as inhibitor of apoptosis proteins (IAPs). It is expressed and controlled during cellular differentiation and development in human beings. Survivin expression has been shown in a number of cancers and has been associated with cancer development.
Objective: In our study, we compared with blood samples as our control and normal- tumoural tissue samples, which obtained from the same tissue of 100 cases diagnosed with colorectal cancer, at Department of Pathology, Istanbul University.
Methods: The present study employed PCR-RFLP to identify the -31 G/C polymorphism in the promoter region of the survivin gene. Distribution of the survivin polymorphism was compared between control and tumoural tissue samples using the chi-square test.
Results: Comparison of all samples revealed that there was significant difference in distribution of survivin promoter -31G/C between control group and tumour and normal tissue of the patient group (p<0.05). When genotypes of the control and tumour tissues were compared according to gender, there was no statistically significant difference in the distribution of survivin promoter -31G/C in females p=0.420 or males p=0.309.
Conclusion: A significant difference was seen in distribution of C allele in tumour tissue compared to normal tissue.

Park M, Lim JW, Kim H
Docoxahexaenoic Acid Induces Apoptosis of Pancreatic Cancer Cells by Suppressing Activation of STAT3 and NF-κB.
Nutrients. 2018; 10(11) [PubMed] Article available free on PMC after 15/10/2019 Related Publications
The ω3-polyunsaturated fatty acid docosahexenoic acid (DHA) is known to induce apoptosis of cancer cells. In this study, DHA was shown to reduce viability of pancreatic cancer cells (PANC-1) by inducing DNA fragmentation, activating caspase-3, and increasing the ratio of Bax/Bcl-2. To determine the DHA mechanism of action, the impact of DHA on the activation of the key signaling proteins epidermal growth factor receptor (EGFR), signal transducer and activator of transcription factor 3 (STAT3), nuclear transcription factor-κB (NF-κB), and IκBα in PANC-1 cells was probed. The observed DHA suppression of NF-κB DNA-binding activity was found to result from reduced IκBα phosphorylation. The observed DHA-induced suppression of STAT3 activation was found to be the result of suppressed EGFR activation, which derives from the inhibitory effect of DHA on the integrity of localization of EGFR to cell membrane lipid rafts. Since the activation of STAT3 and NF-κB mediates the expression of survival genes cyclin D1 and survivin, DHA induced apoptosis by suppressing the STAT3/NF-κB-cyclin D1/survivin axis. These results support the proposal that DHA-induced apoptosis of pancreatic cells occurs via disruption of key pro-cell survival signaling pathways. We suggest that the consumption of DHA-enriched foods could decrease the incidence of pancreatic cancer.

Phiboonchaiyanan PP, Petpiroon N, Sritularak B, Chanvorachote P
Phoyunnanin E Induces Apoptosis of Non-small Cell Lung Cancer Cells
Anticancer Res. 2018; 38(11):6281-6290 [PubMed] Related Publications
BACKGROUND/AIM: Lung cancer is by far the most common cause of cancer mortality, accounting for nearly 20% of all global cancer deaths. Therefore, potent and effective compounds for treatment of this cancer type are essential. Phoyunnanin E, isolated from Dendrobium venustum (Orchidaceae), has promising pharmacological activities; however, it is unknown if phoyunnanin E affects apoptosis of lung cancer cells.
MATERIALS AND METHODS: The apoptosis-inducing activity of phoyunnanin E on H460 lung cancer cells was investigated by Hoechst 33342, and annexin V-fluorescein isothiocyanate/propidium iodide staining. The underlying mechanism was determined via monitoring apoptosis-regulatory proteins by western blot analysis. The apoptotic effect of the compound was confirmed in H23 lung cancer cells.
RESULTS: Phoyunnanin E significantly induced apoptotic cell death of H460 lung cancer cells, as indicated by condensed and fragmented nuclei with the activation of caspase-3 and -9 and poly (ADP-ribose) polymerase cleavage. Phoyunnanin E mediated apoptosis via a p53-dependent pathway by increasing the accumulation of cellular p53 protein. As a consequence, anti-apoptotic proteins including induced myeloid leukemia cell differentiation protein (MCL1) and B-cell lymphoma 2 (BCL2) were found to be significantly depleted, while pro-apoptotic BCL-2-associated X protein (BAX) protein was up-regulated. Furthermore, it was found that expression of an inhibitor of apoptosis, survivin, markedly reduced in response to phoyunnanin E treatment. The apoptosis-inducting effect was also found in phoyunnanin E-treated H23 lung cancer cells.
CONCLUSION: These results indicate the promising effect of phoyunnanin E in induction of apoptosis, that may be useful for the development of novel anticancer agents.

Bi Y, Lee RJ, Wang X, et al.
Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy.
Int J Nanomedicine. 2018; 13:5811-5822 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Purpose: A liposome-based siRNA-drug combination was evaluated as a potential therapeutic strategy to improve the curative effect.
Methods: A topoisomerase inhibitor SN38 prodrug was combined with a survivin siRNA through codelivery using transferrin (Tf)-L-SN38/P/siRNA. In this combination, SN38 was conjugated to the cell penetrating peptide TAT through a polyethylene glycol (PEG) linker to synthesize TAT-PEG-SN38. The amphiphilic TAT-PEG-SN38 was used as an ingredient of liposomes to improve the cellular uptake. Protamine was added to form an electrostatic complex with siRNA in the core of the liposomes. Tf was introduced to enable tumor cell targeting of liposomes (Tf-L-SN38/P/siRNA).
Results: Tf-L-SN38/P/siRNA exhibited a particle size of 148 nm and a ζ-potential of +7.8 mV. The cellular uptake and antitumor activity were dependent on Tf receptor targeting, TAT-PEG-SN38, and siRNA codelivery. Tf-L-SN38/P/siRNA was shown to be considerably more effective than liposomes carrying individual components. This combination induced potent tumor inhibition (76.8%) in HeLa cell xenograft tumor-bearing nude mice.
Conclusion: These data indicated that Tf-L-SN38/P/siRNA was an effective system for codelivery of SN38 and a survivin siRNA and that its therapeutic potential deserved further evaluation.

Kafadar D, Yaylim I, Kafadar AM, et al.
Investigation of
Anticancer Res. 2018; 38(10):5991-5998 [PubMed] Related Publications
BACKGROUND/AIM: The single nucleotide polymorphism -31C/G identified in the survivin gene promoter seems to be associated with over-expression of survivin, an anti-apoptotic protein. In gliomas, increased survivin expression correlated with decreased survival. The aim of the study was to investigate whether survivin gene polymorphism associates with benign and malignant brain tumors and whether it affects survivin serum levels.
PATIENTS AND METHODS: Survivin polymorphism -31C>G was genotyped in 82 patients with brain tumors and 65 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and survivin levels were evaluated by enzyme-linked immuno sorbent assay (ELISA) in patients and controls.
RESULTS: Serum survivin levels in patients with malignant tumors were higher than patients with benign tumors (p<0.001). Survivin levels in patients with malignant glial tumors and the frequency of the GG genotype were higher than in patients with benign tumors (p=0.04) and controls (p=0.05). The prevelance of the survivin gene promoter polymorphism -31C>G did not differ between patients and controls.
CONCLUSION: Survivin promoter -31C>G gene polymorphism seems to be associated with serum survivin levels in brain tumors of different grades and histologies.

Han L, Yuan B, Shimada R, et al.
Cytocidal effects of arenobufagin and hellebrigenin, two active bufadienolide compounds, against human glioblastoma cell line U-87.
Int J Oncol. 2018; 53(6):2488-2502 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Glioblastoma is the most common and lethal intracranial tumor type, characterized by high angiogenic and infiltrative capacities. To provide a novel insight into therapeutic strategies against glioblastoma, the cytotoxicity of arenobufagin and hellebrigenin was investigated in the human glioblastoma cell line, U-87. Similar dose-dependent cytotoxicity was observed in the cells, whereas no detectable toxicity was confirmed in mouse primary astrocytes. Treatment with each drug downregulated the expression levels of Cdc25C, Cyclin B1 and survivin, which occurred in parallel with G2/M phase arrest. Necrotic-like cell death was only observed in the cells treated with a relatively high concentration (>100 ng/ml). These results indicate that the two drugs exhibited distinct cytotoxicity against cancerous glial cells with high potency and selectivity, suggesting that growth inhibition associated with G2/M phase arrest and/or necrosis were attributed to their toxicities. Activation of the p38 mitogen activated protein kinase (MAPK) signaling pathway was also observed in treated cells. Notably, a specific inhibitor of p38 MAPK, SB203580, itself caused a significant decrease in cell viability, and further enhanced the cytotoxicity of the two drugs, suggesting an important pro-survival role for p38 MAPK. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a novel combination regimen of arenobufagin/hellebrigenin plus a p38 MAPK inhibitor may improve the efficacy of the two drugs, and may provide more therapeutic benefits to patients with glioblastoma. The qualitative assessment demonstrated the existence of arenobufagin in the cerebrospinal fluid of arenobufagin-treated rats, supporting its clinical application.

Ghavifekr Fakhr M, Rezaie Kahkhaie K, Shanehbandi D, et al.
Scrophularia Atropatana Extract Reverses TP53 Gene Promoter Hypermethylation and Decreases Survivin Antiapoptotic Gene Expression in Breast Cancer Cells
Asian Pac J Cancer Prev. 2018; 19(9):2599-2605 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Background: In many cases of breast cancer, the aberrant methylation of TP53 gene leads to uncontrolled cell proliferation and apoptosis inhibition. Moreover, expression of oncogenes which are under the control of P53 protein could be altered. Survivin as a conspicuous example of this category plays important roles in tumorigenesis, drug resistance and apoptosis inhibition. The present study was done to reveal the effects of Scrophularia atropatana extract on epigenetic situation of TP53 gene promoter and the expression levels of anti-apoptotic gene, survivin and its potential for production of cancer epi-drugs. Methods: Cytotoxic effect of dichloromethane extracts of Scrophularia plant on MCF-7 cell line was assessed in our previous study. Cell death ELISA (enzyme-linked immunosorbent assay) and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) tests were used to investigate the occurrence of apoptosis in the treated cells. Methylation Specific PCR (MSP) was employed to assess the changes in methylation status of the TP53 gene promoter. Furthermore, quantitative real time PCR was utilized to evaluate the resulting changes in TP53 and survivin genes expression. Results: Cell death ELISA and TUNEL assays confirmed the occurrence of apoptosis. MSP test revealed a significant change in the methylation status of TP53 promoter. QRT-PCR showed an increased TP53 gene expression in the treated cells while a significant decrease in survivin mRNA was evident. Conclusions: According to the outcomes, dichloromethane extract of S. atropatana returned the TP53 gene promoter hypermethylation to normal state. This plant could be a promising source for production of epi-drugs due to its apoptotic effects and reversal of TP53 epigenetic alterations.

Wang B, Li X, Zhao G, et al.
miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway.
J Exp Clin Cancer Res. 2018; 37(1):235 [PubMed] Article available free on PMC after 15/10/2019 Related Publications
BACKGROUND: We previously reported that miR-203 functions as a tumor suppressor in ovarian cancer cells by directly targeting transcription factor Snai2 and inhibiting epithelial to mesenchymal transition (EMT), whereas BIRC5/survivin promotes EMT. In this study, we tested our hypothesis that miR-203 inhibits ovarian tumor metastasis by suppressing EMT through targeting BIRC5, using an orthotopic ovarian cancer mouse model.
METHODS: We overexpressed miR-203 in ovarian cancer SKOV3 and OVCAR3 cells using a lentiviral vector and examined cell migration and invasion using transwell plates. The small molecule inhibitor, YM155, was used to inhibit survivin expression. miR-203-expressing and control SKOV3 cells were intrabursally injected into immunocompromised NSG female mice. Primary tumors in ovaries and metastatic tumors were collected to determine the expression of survivin and EMT markers using Western blot and immunostaining.
RESULTS: Overexpression of miR-203 inhibits EMT by targeting BIRC5 in ovarian cancer SKOV3 and OVCAR3 cells. miR-203 expression enhances the ability of the survivin inhibitor YM155 to reduce tumor cell migration and invasion in vitro. We further showed that miR-203 expression attenuated the TGFβ pathway in both SKOV3 and OVCAR3 cells. miR-203 expression also inhibited primary tumor growth in ovaries and metastatic tumors in multiple peritoneal organs including liver and spleen.
CONCLUSION: miR-203 inhibits ovarian tumor metastasis by targeting BIRC5/survivin and attenuating the TGFβ pathway.

Ahmed W, Malik MFA, Saeed M, Haq F
Copy number profiling of Oncotype DX genes reveals association with survival of breast cancer patients.
Mol Biol Rep. 2018; 45(6):2185-2192 [PubMed] Related Publications
Copy number variations (CNVs) are key contributors in breast cancer initiation and progression. However, to date, no CNV-based gene signature is developed for breast cancer. 21-gene Oncotype DX, a clinically validated signature, was identified using only RNA expression data in breast cancer patients. In this study, we evaluated whether CNVs of Oncotype DX genes can be used to predict the prognosis of breast cancer patients. Transcriptomic data of 547 and genomic data of 816 of breast cancer patients were downloaded from The Cancer Genome Atlas database. To establish the prognostic relevance between the CNVs of Oncotype DX genes and clinicopathological features, statistical analysis including Pearson Correlation, Fisher-exact, Chi square, Kaplan-Meier survival and Cox regression analyses were performed. 86% genes showed positive CNV-expression correlation. CNVs in 52% and 47.6% genes showed association with ER+ and PR+ status, respectively. 71% of the genes (including ERBB2, CTSV, CD68, GRB7, MKI67, MMP1, PGR, RPLP0, TFRC, BAG1, BCL2, BIRC5, FLNB, GSTM1 and SCUBE2) showed association with poor overall survival. 14% of the genes (including CTSV, RPLP0 and BIRC5) genes showed association with disease free survival. Cox regression analysis revealed ESR1, metastasis and node stage as independent prognostic factors for overall survival of breast cancer patients. The results suggested that CNV-based assay of Oncotype DX genes can be used to predict the survival of breast cancer patients. In future, identifying new gene signatures for better breast cancer prognosis using CNV level information will be worth investigating.

Aşık E, Aslan TN, Güray NT, Volkan M
Cellular uptake and apoptotic potential of rhenium labeled magnetic protein cages in MDA-MB-231 cells.
Environ Toxicol Pharmacol. 2018; 63:127-134 [PubMed] Related Publications

Troiano G, Guida A, Aquino G, et al.
Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma.
Int J Mol Sci. 2018; 19(9) [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene

Hehlgans S, Booms P, Güllülü Ö, et al.
Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib.
Int J Mol Sci. 2018; 19(9) [PubMed] Article available free on PMC after 15/10/2019 Related Publications
Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53-binding protein 1 (γH2AX/53BP1) foci in vismodegib- and radiation-treated cells was associated with a significant radiosensitization of both cell lines. In summary, these findings indicate that inhibition of the Hedgehog signaling pathway may increase cellular radiation response in BCC and HNSCC cells.

Xie W, Hao J, Zhang K, et al.
Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M phase arrest and apoptosis promotion.
Biochem Biophys Res Commun. 2018; 503(4):2758-2763 [PubMed] Related Publications
The Vestigial-Like Family Member 4 (VGLL4) functions as a native inhibitor of cell proliferation and tumor growth through multiple signaling pathways. We first discovered that VGLL4 causes G2/M phase arrest in hepatocellular carcinoma (HCC) cells. Then, we designed a novel survivin-regulated oncolytic adenovirus Ad-sp-VGLL4 carrying the VGLL4 gene. Ad-sp-VGLL4 exerted high HCC-targeting-selectivity but is less harmful to normal cells. This adenovirus construction enhanced antitumor activity due to G2/M phase arrest and enhanced apoptosis. It's also indicated that Ad-sp-VGLL4 could suppress the growth of transplanted tumor of HCC in vivo experiment. Taken together, our results suggest that Ad-sp-VGLL4 possesses strong antitumor capacity and has great potential use for HCC therapy.

Further References

Suzuki A, Ito T, Kawano H, et al.
Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death.
Oncogene. 2000; 19(10):1346-53 [PubMed] Related Publications
Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.

Mahotka C, Wenzel M, Springer E, et al.
Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties.
Cancer Res. 1999; 59(24):6097-102 [PubMed] Related Publications
Recently, a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer. Therefore, we analyzed the expression of survivin in human renal cell carcinomas (RCCs), known to be largely resistant to chemotherapy. Northern blot analysis and RT-PCR revealed survivin expression in newly established RCC cell lines (n = 11) of all major histological types. Moreover, we identified two novel splice variants of survivin, lacking exon 3 (survivin-deltaEx3) or retaining a part of intron 2 as a cryptic exon (survivin-2B). Both sequence alterations cause marked changes in the structure of the corresponding proteins, including structural modifications of the baculovirus inhibitor of apoptosis protein repeat domain. The role of the novel isoforms in the regulation of apoptosis was assessed in transfection experiments, showing conservation of antiapoptotic properties for survivin-deltaEx3 and a markedly reduced antiapoptotic potential for survivin-2B. In conclusion, our observations suggest a complex regulatory balance between the different isoforms of survivin, which might determine the response to proapoptotic stimuli, not only in human RCCs but also in fetal tissues and other types of cancer.

Li F, Ambrosini G, Chu EY, et al.
Control of apoptosis and mitotic spindle checkpoint by survivin.
Nature. 1998; 396(6711):580-4 [PubMed] Related Publications
Progression of the cell cycle and control of apoptosis (programmed cell death) are thought to be intimately linked processes, acting to preserve homeostasis and developmental morphogenesis. Although proteins that regulate apoptosis have been implicated in restraining cell-cycle entry and controlling ploidy (chromosome number), the effector molecules at the interface between cell proliferation and cell survival have remained elusive. Here we show that a new inhibitor of apoptosis (IAP) protein, survivin, is expressed in the G2/M phase of the cell cycle in a cycle-regulated manner. At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of survivin's anti-apoptosis function and increased caspase-3 activity, a mechanism involved in cell death, during mitosis. These results indicate that survivin may counteract a default induction of apoptosis in G2/M phase. The overexpression of survivin in cancer may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis.

Ambrosini G, Adida C, Altieri DC
A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.
Nat Med. 1997; 3(8):917-21 [PubMed] Related Publications
Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.

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