LASP1

Gene Summary

Gene:LASP1; LIM and SH3 protein 1
Aliases: MLN50, Lasp-1
Location:17q12
Summary:This gene encodes a member of a subfamily of LIM proteins, characterized by a LIM motif and a domain of Src homology region 3, and also a member of the nebulin family of actin-binding proteins. The encoded protein is a cAMP and cGMP dependent signaling protein and binds to the actin cytoskeleton at extensions of the cell membrane. The encoded protein has been linked to metastatic breast cancer, hematopoetic tumors such as B-cell lymphomas, and colorectal cancer. [provided by RefSeq, Oct 2012]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:LIM and SH3 domain protein 1
Source:NCBIAccessed: 30 August, 2019

Ontology:

What does this gene/protein do?
Show (8)

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 (5)

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

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

Latest Publications: LASP1 (cancer-related)

Liu Y, Gao Y, Li D, et al.
LASP1 promotes glioma cell proliferation and migration and is negatively regulated by miR-377-3p.
Biomed Pharmacother. 2018; 108:845-851 [PubMed] Related Publications
Glioma is one of the most aggressive and lethal human cancers with a low cure rate. LASP1 plays an oncogenic role in multiple human cancers; however, its role in glioma remains largely unknown. Here, we found that LASP1 was highly expressed in glioma tissue samples. Functionally, knockdown of LASP1 significantly suppressed glioma cell proliferation and migration in vitro and tumorigenicity in vivo. These effects were found to be mechanistically associated with suppression of AKT activity. Furthermore, we identified LASP1 as a direct target of miR-377-3p. Overexpression of miR-377-3p reduced the expression of LASP1 and suppressed the proliferation and migration of glioma cells. Restoration of LASP1 expression in miR-377-3p-overexpressing cells attenuated the inhibition of glioma cell malignancy and reversed the dephosphorylation of AKT. Taken together, our results suggest that LASP1 activates the PI3K/AKT signaling pathway and is downregulated by miR-377-3p during glioma progression. These data provide a new possible therapeutic target in glioma.

Davaadelger B, Murphy AR, Clare SE, et al.
Mechanism of Telapristone Acetate (CDB4124) on Progesterone Receptor Action in Breast Cancer Cells.
Endocrinology. 2018; 159(10):3581-3595 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Progesterone is a steroid hormone that plays an important role in the breast. Progesterone exerts its action through binding to progesterone receptor (PR), a transcription factor. Deregulation of the progesterone signaling pathway is implicated in the formation, development, and progression of breast cancer. Next-generation selective progesterone receptor modulators (SPRMs) have potent antiprogestin activity and are selective for PR, reducing the off-target effects on other nuclear receptors. To date, there is limited information on how the newer generation of SPRMs, specifically telapristone acetate (TPA), affect PR function at the molecular level. In this study, T47D breast cancer cells were used to investigate the molecular mechanism by which TPA antagonizes PR action. Global profiling of the PR cistrome and interactome was done with chromatin immunoprecipitation sequencing (ChIP-seq) and rapid immunoprecipitation mass spectrometry. Validation studies were done on key genes and interactions. Our results demonstrate that treatment with the progestin (R5020) alone resulted in robust PR recruitment to the chromatin, and addition of TPA reduced PR recruitment globally. TPA significantly changed coregulator recruitment to PR compared with R5020. Upon conservative analysis, three proteins (TRPS1, LASP1, and AP1G1) were identified in the R5020+TPA-treated group. Silencing TRPS1 with small interfering RNA increased PR occupancy to the known PR regulatory regions and attenuated the inhibition of gene expression after TPA treatment. TRPS1 silencing alleviated the inhibition of proliferation by TPA. In conclusion, TPA decreases PR occupancy on chromatin and recruits coregulators such as TRPS1 to the PR complex, thereby regulating PR target gene expression and associated cellular responses.

Hu Z, Wang X, Cui Y, et al.
LASP1 in Tumor and Tumor Microenvironment.
Curr Mol Med. 2017; 17(8):541-548 [PubMed] Related Publications
The growing evidence shows that LIM and SH3 Domain Protein 1 (LASP1) is a multi-functional protein that plays important role in forming cytoskeleton and prognostic marker in different cancers. LASP1 expression is correlated with the grade, size, and the metastasis of tumor in clinical samples. And the upregulation of LASP1 facilitates tumor cells proliferation, migration, and invasion perhaps through the interaction with cytoskeleton and increased nuclear translocation. The underlying mechanism of LASP1 on tumor is still in the initial stage; therefore, the signaling pathways in various tumors are specifically summarized to deepen the biological understanding of LASP1. This article systematically summarizes the current status of knowledge regarding the contribution of LASP1 in physiological and pathological processes, especially the progress in tumor. This article also gives an emphasized overview of LASP1 on the correlation with tumor microenvironment.

Sui Y, Zhang X, Yang H, et al.
MicroRNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1.
Oncol Rep. 2018; 39(2):473-482 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Many microRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in human cancers including breast cancer. However, the molecular mechanism of miR-133a underlying the malignant progression of breast cancer still remains obscure. In the present study we observed that the expression of miR-133a was significantly downregulated in breast cancer tissues and cell lines, when compared with adjacent non-tumor tissues and normal breast cell line, respectively. Reduced miR-133a levels were significantly associated with advanced clinical stage, lymph node metastasis, as well as shorter survival time of patients with breast cancer. Restoration of miR-133a expression led to significant decrease in the proliferation, migration, and invasion of SK-BR-3 and MDA-MB-231 cells in vitro, as well as in tumor xenograft growth in nude mice. Luciferase reporter gene assay data identified LASP1 as a target gene of miR-133a, and the expression of LASP1 was negatively regulated by miR-133a in breast cancer cells. LASP1 was significantly upregulated in breast cancer tissues and cell lines, and its upregulation was significantly associated with disease progression. siRNA-induced LASP1 downregulation caused a significant reduction in breast cancer cell proliferation, migration and invasion. Furthermore, overexpression of LASP1 impaired the suppressive effects of miR-133a upregulation on the proliferation, migration and invasion of SK-BR-3 and MDA-MB-231 cells. In summary, the present study demonstrates that miR-133a acts as a tumor suppressor in breast cancer partly at least via targeting LASP1, and thus suggests that the miR-133a/LASP1 axis may become a potential therapeutic target for breast cancer.

Shi J, Guo J, Li X
Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer.
Int J Oncol. 2018; 52(1):179-188 [PubMed] Related Publications
Lung cancer accounts for most cancer-related deaths worldwide. However, the underlying mechanism by which it mediates the progression of lung cancer remains unclear. Expression of LASP-1 (LIM and SH3 protein 1) was evaluated in lung cancer tissues and tumor-adjacent normal tissues using immunohistochemistry and western blotting. Functional studies have shown that siRNA-mediated silencing of LASP-1 in human lung cancer cells and reduced cell proliferation, migration, and invasion. Flow cytometry and immunofluorescence staining also revealed that rate of cell apoptosis was increased after knockdown of expression of LASP-1, thereby suggesting that LASP-1 may function as an oncogene during lung cancer progression. SOX9 is an important transcription factor, which is involved in the development of several types of human cancer. Further analysis has showed the presence of a consensus-binding site of SOX9 in the promoter region of LASP-1. Mechanistic investigations showed that LASP-1 was transcriptionally activated by SOX9. Through luciferase reporter and ChIP assays, we demonstrated that LASP-1 was a direct target gene of sex determining region Y-box 9 (SOX9). Knockdown of SOX9 expression by RNA interference reduces cell proliferation and induces apoptosis of lung cancer cells, which was consistent with the results obtained from silencing the expression of LASP-1 in NCI‑H1650 cells. Together, these findings indicated that LASP-1, as a downstream target of SOX9, may act as a novel biomarker for lung cancer and plays an important role in cell proliferation, migration, and invasion.

Jiang N, Jiang X, Chen Z, et al.
MiR-203a-3p suppresses cell proliferation and metastasis through inhibiting LASP1 in nasopharyngeal carcinoma.
J Exp Clin Cancer Res. 2017; 36(1):138 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND: miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.
METHODS: The expression level of miR-203a-3p in human NPC tissues and cell lines was detected via real-time PCR (RT-PCR). Cell proliferation, migration and invasion were assessed in vitro by MTT, colony formation and transwell assay, respectively. The function of miR-203a-3p in vivo was detected through NPC xenograft tumor growth and lung metastatic mice model. Dual-luciferase reporter assay was used to identify the direct target of miR-203a-3p.
RESULTS: The expression of miR-203a-3p was decreased in NPC tissues and cell lines in comparison with normal nasopharyngeal tissues and cell line. Ectopic expression of miR-203a-3p inhibited while inhibiting miR-203a-3p expression increased NPC cell proliferation, migration and invasion in vitro. MR-203a-3p overexpression suppressed xenograft tumor growth and lung metastasis in vivo. LASP1 was identified as a direct target of miR-203a-3p, which was confirmed by real-time PCR and western blotting assay. Ectopic expression of LASP1 partially reversed miR-203a-3p-mediated inhibition on proliferation, migration and invasion in NPC cells.
CONCLUSION: Collectively, miR-203a-3p suppresses tumor growth and metastasis through targeting LASP1 in NPC. The newly identified miR-203a-3p/LASP1 pathway provides further insights into the initiation and progression of NPC, which may represent a novel therapeutic target for NPC.

Hu S, Ran Y, Chen W, et al.
MicroRNA-326 inhibits cell proliferation and invasion, activating apoptosis in hepatocellular carcinoma by directly targeting LIM and SH3 protein 1.
Oncol Rep. 2017; 38(3):1569-1578 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is the fifth-most common cancer and third leading cause of cancer-related deaths worldwide. Increasing evidence indicates that dysregulation of microRNAs is often observed in HCC, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. Recently, microRNA-326 (miR-326) has been demonstrated to play important roles in multiple types of human cancer. However, the expression pattern, clinical significance, roles and regulatory mechanisms of miR-326 in HCC have yet to be elucidated. In this study, miR-326 was frequently downregulated in HCC tissues and cell lines. Low miR-326 expression was significantly associated with the TNM stage, differentiation and lymph node metastasis of HCC patients. Further functional assays demonstrated that the recovered miR-326 expression inhibited HCC cell proliferation and invasion and activated cell apoptosis in vitro. In addition, LIM and SH3 protein 1 (LASP1) was identified as a direct target gene of miR-326 in HCC. Furthermore, LASP1 was upregulated in HCC tissues and cell lines. The expression level of LASP1 mRNA was inversely correlated with that of miR-326 in HCC tissues. Moreover, LASP1 silencing elicited effects similar to miR-326 overexpression on HCC cells, and LASP1 upregulation markedly reversed the effects of miR-326 overexpression on HCC cells. These results revealed that miR-326 suppressed the progression of HCC by directly targeting LASP1. Therefore, miR-326 may be used as a potential therapeutic target for the treatment of patients with HCC.

Ruggieri V, Agriesti F, Tataranni T, et al.
Paving the path for invasion: The polyedric role of LASP1 in cancer.
Tumour Biol. 2017; 39(6):1010428317705757 [PubMed] Related Publications
Although usually referred to as a structural actin-binding protein, LIM and SH3 domain-containing protein may actually be dynamically involved in the control of a wide spectrum of cellular processes, by virtue of its interaction with several molecular partners. Alongside being ubiquitously expressed in physiological conditions, LIM and SH3 domain-containing protein is overexpressed in a growing number of human cancers, in which it may actively contribute to their aggressiveness by promoting cell proliferation and migration. In view of the recent findings, implicating the protein in cancer progression, we discuss here the most relevant discoveries highlighting the role of this versatile protein in various human tumors. The correlation between LIM and SH3 domain-containing protein expression levels in cancer and the poor outcome and metastatic behavior of tumors denotes the clinical significance of this protein and hints its potential value as a new cancer prognostic or even diagnostic biomarker. This may be decisive not only to optimize existing pharmacological regimes but also to delineate novel, more efficacious therapeutic and/or preventive approaches.

Moazzeni H, Najafi A, Khani M
Identification of direct target genes of miR-7, miR-9, miR-96, and miR-182 in the human breast cancer cell lines MCF-7 and MDA-MB-231.
Mol Cell Probes. 2017; 34:45-52 [PubMed] Related Publications
Some microRNAs have carcinogenic or tumor suppressive effects in breast cancer, which is the most common cancer in women worldwide. MiR-7 and miR-9 are tumor suppressor microRNAs, which induce apoptosis and inhibit proliferation in breast cancer cells. Moreover, miR-96 and miR-182 are onco-microRNAs that increase proliferation, migration, and tumorigenesis in breast cancer cells. This study aimed to identify the direct target genes of these four microRNAs in the human breast cancer cell lines MCF-7 and MDA-MB-231. Initially, bioinformatics tools were used to identify the target genes that have binding sites for miR-7, MiR-9, MiR-96, and miR-182 and are also associated with breast cancer. Subsequently, the findings of the bioinformatics analysis relating to the effects of these four microRNAs on the 3'-UTR activity of the potential target genes were confirmed using the dual luciferase assay in MCF-7 and MDA-MB-231 cells co-transfected with the vectors containing 3'-UTR segments of the target genes downstream of a luciferase coding gene and each of the microRNAs. Finally, the effects of microRNAs on the endogenous expression of potential target genes were assessed by the overexpression of each of the four microRNAs in MCF-7 and MDA-MB-231 cells. Respectively, three, three, three, and seven genes were found to have binding sites for miR-7, miR-9, miR-96, and miR-182 and were associated with breast cancer. The results of empirical studies including dual luciferase assays and real-time PCR confirmed that miR-7 regulates the expression of BRCA1 and LASP1; MiR-9 regulates the expression of AR; miR-96 regulates the expression of ABCA1; and miR-182 regulates the expression of NBN, TOX3, and LASP1. Taken together, our results suggest that the tumor suppressive effects of miR-7 may be mediated partly by regulating the expression of BRCA1 as a tumor suppressor gene in breast cancer. In addition, this microRNA and miR-182 may have effects on the nodal-positivity and tumor size of breast carcinoma through the regulation of LASP1. The tumor suppressive functions of miR-9 may be mediated partly by suppressing the expression of AR-an oncogene in breast cancer. Moreover, miR-96 may play an oncogenic role in breast cancer by suppressing the apoptosis through the regulation of ABCA1.

Dyshlovoy SA, Otte K, Venz S, et al.
Proteomic-based investigations on the mode of action of the marine anticancer compound rhizochalinin.
Proteomics. 2017; 17(11) [PubMed] Related Publications
Rhizochalinin (Rhiz) is a novel marine natural sphingolipid-like compound, which shows promising in vitro and in vivo activity in human castration-resistant prostate cancer. In the present study, a global proteome screening approach was applied to investigate molecular targets and biological processes affected by Rhiz in castration-resistant prostate cancer. Bioinformatical analysis of the data predicted an antimigratory effect of Rhiz on cancer cells. Validation of proteins involved in the cancer-associated processes, including cell migration and invasion, revealed downregulation of specific isoforms of stathmin and LASP1, as well as upregulation of Grp75, keratin 81, and precursor IL-1β by Rhiz. Functional analyses confirmed an antimigratory effect of Rhiz in PC-3 cells. Additionally, predicted ERK1/2 activation was confirmed by Western blotting analysis, and revealed prosurvival effects in Rhiz-treated prostate cancer cells indicating a potential mechanism of resistance. A combination of Rhiz with MEK/ERK inhibitors PD98059 (non-ATP competitive MEK1 inhibitor) and FR180204 (ATP-competitive ERK1/2 inhibitor) resulted in synergistic effects. This work provides further insights into the molecular mechanisms underlying Rhiz bioactivity. Furthermore, our research is exemplary for the ability of proteomics to predict drug targets and mode of action of natural anticancer agents.

Li PD, Hu JL, Ma C, et al.
Upregulation of the long non-coding RNA PVT1 promotes esophageal squamous cell carcinoma progression by acting as a molecular sponge of miR-203 and LASP1.
Oncotarget. 2017; 8(21):34164-34176 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Long non-coding RNAs are a group of non-coding RNAs longer than 200 nucleotides and possess diverse functions and exhibit exquisite cell-specific and developmental dynamic expression patterns. The role of the long non-coding RNA PVT1 in esophageal squamous cell carcinoma remains unsolved. Here, we showed that PVT1 expression is significantly up-regulated in ESCC tumor samples compared with their normal counterparts. Knockdown of PVT1 suppressed tumor growth in vitro and in vivo. Further studies revealed that silence of PVT1 lead to up-regulation of miR-203, and vice versa. Moreover, LASP1 was found to be downregulated after knockdown of PVT1 and overexpression of LASP1 attenuated the tumor-suppressive roles of PVT1 knockdown. Our results suggest that PVT1 promote ESCC progression via functioning as a molecular sponge for miR-203 and LASP1 and provide the first evidence of dysregulated PVT1/miR-203/LASP1 axis in ESCC.

Li W, Li H, Zhang L, et al.
Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity.
J Biol Chem. 2017; 292(14):5801-5813 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals in genome-wide sequencing studies. Some of these RNAs have been consistently conserved during the evolution of species and could presumably function in important biologic processes. Therefore, we measured the levels of 26 highly conserved lincRNAs in a total of 176 pairs of endometrial carcinoma (EC) and surrounding non-tumor tissues of two distinct Chinese populations. Here, we report that a lincRNA,

Li H, Xiang Z, Liu Y, et al.
MicroRNA-133b Inhibits Proliferation, Cellular Migration, and Invasion via Targeting LASP1 in Hepatocarcinoma Cells.
Oncol Res. 2017; 25(8):1269-1282 [PubMed] Related Publications
MicroRNAs (miRs), a class of small noncoding RNAs, are key gene regulators through inducing translational repression or degradation of their target genes. However, the regulatory mechanism of miR-133b underlying hepatocellular carcinoma (HCC) growth and metastasis remains largely unclear. Here we found that miR-133b was significantly downregulated in HCC tissues and cell lines. Moreover, low miR-133b levels were significantly associated with the malignant progression of HCC. LASP1, upregulated in HCC tissues and cell lines, was then identified as a novel target of miR-133b in HCC HepG2 and Hep3B cells. Moreover, the increased expression of LASP1 was associated with HCC progression. An in vitro study showed that overexpression of miR-133b inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Similarly, knockdown of LASP1 reduced HepG2 and Hep3B cell proliferation, migration, and invasion. Furthermore, overexpression of LASP1 attenuated the suppressive effect of miR-133b on the malignant phenotypes of HepG2 and Hep3B cells, suggesting that miR-133b may inhibit HCC growth and metastasis via targeting LASP1. In addition, overexpression of miR-133b inhibits tumor growth of HepG2 and Hep3B cells in vivo. Therefore, the miR-133b/LASP1 axis may become a potential target for the treatment of HCC.

Gao W, Han J
Silencing of LIM and SH3 Protein 1 (LASP-1) Inhibits Thyroid Cancer Cell Proliferation and Invasion.
Oncol Res. 2017; 25(6):879-886 [PubMed] Related Publications
LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein that was first identified in breast cancer and then reported to be involved in cell proliferation and migration. Many studies have demonstrated the essential role of LASP-1 in cancer progression. However, there have been no studies on the association of LASP-1 with thyroid cancer. In this study, we investigated the expression pattern and biological function of LASP-1 in thyroid cancer. We found that LASP-1 was highly expressed in thyroid cancer tissues and cell lines. LASP-1 silencing had antiproliferative and anti-invasive effects on thyroid cancer cells. Moreover, tumor xenograft experiments showed that LASP-1 silencing suppressed thyroid cancer cell growth in vivo. We also demonstrated that LASP-1 silencing decreased the protein expression of p-PI3K and p-Akt. In conclusion, these findings suggest LASP-1 to be an oncogene and a potential therapeutic target in thyroid cancer.

Andrews MC, Cursons J, Hurley DG, et al.
Systems analysis identifies miR-29b regulation of invasiveness in melanoma.
Mol Cancer. 2016; 15(1):72 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
BACKGROUND: In many cancers, microRNAs (miRs) contribute to metastatic progression by modulating phenotypic reprogramming processes such as epithelial-mesenchymal plasticity. This can be driven by miRs targeting multiple mRNA transcripts, inducing regulated changes across large sets of genes. The miR-target databases TargetScan and DIANA-microT predict putative relationships by examining sequence complementarity between miRs and mRNAs. However, it remains a challenge to identify which miR-mRNA interactions are active at endogenous expression levels, and of biological consequence.
METHODS: We developed a workflow to integrate TargetScan and DIANA-microT predictions into the analysis of data-driven associations calculated from transcript abundance (RNASeq) data, specifically the mutual information and Pearson's correlation metrics. We use this workflow to identify putative relationships of miR-mediated mRNA repression with strong support from both lines of evidence. Applying this approach systematically to a large, published collection of unique melanoma cell lines - the Ludwig Melbourne melanoma (LM-MEL) cell line panel - we identified putative miR-mRNA interactions that may contribute to invasiveness. This guided the selection of interactions of interest for further in vitro validation studies.
RESULTS: Several miR-mRNA regulatory relationships supported by TargetScan and DIANA-microT demonstrated differential activity across cell lines of varying matrigel invasiveness. Strong negative statistical associations for these putative regulatory relationships were consistent with target mRNA inhibition by the miR, and suggest that differential activity of such miR-mRNA relationships contribute to differences in melanoma invasiveness. Many of these relationships were reflected across the skin cutaneous melanoma TCGA dataset, indicating that these observations also show graded activity across clinical samples. Several of these miRs are implicated in cancer progression (miR-211, -340, -125b, -221, and -29b). The specific role for miR-29b-3p in melanoma has not been well studied. We experimentally validated the predicted miR-29b-3p regulation of LAMC1 and PPIC and LASP1, and show that dysregulation of miR-29b-3p or these mRNA targets can influence cellular invasiveness in vitro.
CONCLUSIONS: This analytic strategy provides a comprehensive, systems-level approach to identify miR-mRNA regulation in high-throughput cancer data, identifies novel putative interactions with functional phenotypic relevance, and can be used to direct experimental resources for subsequent experimental validation. Computational scripts are available: http://github.com/uomsystemsbiology/LMMEL-miR-miner.

Sun W, Guo L, Shao G, et al.
Suppression of LASP-1 attenuates the carcinogenesis of prostatic cancer cell lines: Key role of the NF-κB pathway.
Oncol Rep. 2017; 37(1):341-347 [PubMed] Related Publications
Prostate cancer (PCa) is one of the most frequently diagnosed cancers among males worldwide and causes a considerable number of deaths each year. One of the newly explored targets for the development of therapies against PCa is LIM and SH3 protein 1 (LASP-1). In the present study, the function of LASP-1 in the oncogenesis and metastasis of PCa was investigated using a series of in vitro experiments. Moreover, the mechanism through which LASP-1 exerted its effect on the carcinogenesis of PCa was also explored. The expression levels of LASP-1 in clinical PCa specimens were determined both at the mRNA and protein levels. Afterwards, the activity of LASP-1 in human PCa cell lines PC3 and DU145 was inhibited using a short hairpin RNA (shRNA) interfering method. The effects of LASP-1 knockdown on the cell growth, apoptosis, cell cycle distribution, migration and invasion were assessed. It was demonstrated that the expression of LASP-1 was significantly higher in the clinical PCa tissues than the level in the corresponding para-carcinoma tissues. Following the knockdown of the LASP-1 gene in human PCa cell lines, the viability, migration and invasion of the cancer cells were decreased. It was also demonstrated that the change in the cell viability and motile ability were associated with an induction of cell apoptosis and G1 phase cell cycle arrest. Based on the results of the detection of the expression of NF-κB-related factors, it was indicated that LASP-1 may affect the carcinogenesis of PCa through a NF-κB inhibition-dependent manner. Although the detailed explanation of the mechanism of LASP-1 in the carcinogenesis of PCa requires further elucidation, the present study highlights the potential of LASP-1 as a promising therapeutic target to ameliorate the oncogenesis and metastasis of PCa.

Dejima T, Imada K, Takeuchi A, et al.
Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression.
Prostate. 2017; 77(3):309-320 [PubMed] Related Publications
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO).
METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy. Flow cytometry was used to analyze cell cycle. We designed LASP1 ASO for knockdown of LASP1 in vivo studies.
RESULTS: The expression of LASP1 in TMA was increased after androgen ablation and persisted in castration resistant prostate cancer (CRPC). Also in TMA, compared with LNCaP cell, LASP1 expression is elevated in CRPC cell lines (C4-2 and VehA cells). Interestingly, suppression of AR elevated LASP1 expression conversely, AR activation decreased LASP1 expression. Silencing of LASP1 reduced cell growth through G1 arrest which was accompanied by a decrease of cyclin D1. Forced overexpression of LASP1 promoted cell cycle and induced cell growth which was accompanied by an increase of cyclin D1. Systemic administration of LASP1 ASO with athymic mice significantly inhibited tumor growth in CRPC xenografts.
CONCLUSIONS: These results indicate that LASP1 is negatively regulated by AR at the transcriptional level and promotes tumor growth through induction of cell cycle, ultimately suggesting that LASP1 may be a potential target in prostate cancer treatment. Prostate 77:309-320, 2017. © 2016 Wiley Periodicals, Inc.

Wang LL, Wang L, Wang XY, et al.
MicroRNA-218 inhibits the proliferation, migration, and invasion and promotes apoptosis of gastric cancer cells by targeting LASP1.
Tumour Biol. 2016; 37(11):15241-15252 [PubMed] Related Publications
The present study aims to investigate the effects of microRNA-218 (miR-218) on the proliferation, migration, invasion, and apoptosis of gastric cancer (GC) cells by targeting LIM and SH3 domain protein 1 (LASP1). The GC cells in the logarithmic phase were selected and divided into five groups: the blank group, negative control (NC) group, miR-218 inhibitors group, miR-218 inhibitors + siLASP1 group, and miR-218 mimics + siLASP1 group. The miR-218 expression in each group was also detected by qRT-PCR. The CCK8 assay, Transwell migration, and invasion assays and flow cytometry were performed to determine the effects of miR-218 on cell proliferation, migration, invasion, and apoptosis of GC cells. Western blotting was conducted to measure LASP1 protein expression in GC cells after transfection. The qRT-PCR revealed that the transfection of miR-218 mimics could upregulate the miR-218 expression, and the transfection of miR-218 inhibitors could downregulate the miR-218 expression in the GC cells. Compared with the blank and NC groups, the proliferation, migration, and invasion of GC cells were significantly reduced in the miR-218 mimics, miR-218 inhibitors + siLASP1, and miR-218 mimics + siLASP1 groups but enhanced in the miR-218 inhibitors group. Similarly, compared with the blank and NC groups, the cell apoptosis rates in the miR-218 mimics, miR-218 inhibitors + siLASP1, and the miR-218 mimics + siLASP1 groups were significantly increased, while the miR-218 inhibitors group had a lower apoptosis rate. In conclusion, these results indicate that miR-218 could inhibit the proliferation, migration, and invasion and promote apoptosis of GC cells by downregulating LASP1 expression.

Wang W, Ji G, Xiao X, et al.
Epigenetically regulated miR-145 suppresses colon cancer invasion and metastasis by targeting LASP1.
Oncotarget. 2016; 7(42):68674-68687 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
MiR-145 is a tumor-suppressive microRNA that participates in the malignant progression of colorectal cancer (CRC). Although miR-145 has been reported to inhibit proliferation and to induce apoptosis of CRC cells, the reports about its role in invasion and metastasis are controversial. The regulation of miR-145 its own expression also requires further elucidation. In this study, we firstly found that miR-145 is markedly downregulated in the metastatic tumors of CRC patients. Then through gain- and loss-of function studies, we demonstrated that miR-145 suppresses the invasion and metastasis of CRC cells. We also provided experimental evidences which include direct binding assays and verifications on tissue specimens to confirm that LIM and SH3 protein 1 (LASP1) is a direct target of miR-145. Furthermore, we identified the core promoter regions of miR-145 and observed the cooperation between histone methylation and transcription factors through binding to these core promoter regions to regulate the expression of miR-145 in CRC cells. Our study provides an insight into the regulatory network in CRC cells, thus offering new targets for treating CRC patients.

Endres M, Kneitz S, Orth MF, et al.
Regulation of matrix metalloproteinases (MMPs) expression and secretion in MDA-MB-231 breast cancer cells by LIM and SH3 protein 1 (LASP1).
Oncotarget. 2016; 7(39):64244-64259 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane thereby enabling metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cell lines.By analyzing microarray data of in-house generated control and LASP1-depleted MDA-MB-231 breast cancer cells, we observed downregulation of MMP1, -3 and -9 upon LASP1 depletion. This was confirmed by Western blot analysis. Conversely, rescue experiments restored in part MMP expression and secretion. The regulatory effect of LASP1 on MMP expression was also observed in BT-20 breast cancer cells as well as in prostate and bladder cancer cell lines.In line with bioinformatic FunRich analysis of our data, which mapped a high regulation of transcription factors by LASP1, public microarray data analysis detected a correlation between high LASP1 expression and enhanced c-Fos levels, a protein that is part of the transcription factor AP-1 and known to regulate MMP expression. Compatibly, in luciferase reporter assays, AP-1 showed a decreased transcriptional activity after LASP1 knockdown.Zymography assays and Western blot analysis revealed an additional promotion of MMP secretion into the extracellular matrix by LASP1, thus, most likely, altering the microenvironment during cancer progression.The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential of LASP1 overexpressing aggressive tumor cells in earlier studies.

Fjeldbo CS, Aarnes EK, Malinen E, et al.
Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer Patients.
PLoS One. 2016; 11(5):e0156259 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Hypoxia is an adverse factor in cervical cancer, and hypoxia-related gene expression could be a powerful biomarker for identifying the aggressive hypoxic tumors. Reverse transcription quantitative PCR (RT-qPCR) is a valuable method for gene expression studies, but suitable reference genes for data normalization that are independent of hypoxia status and clinical parameters of cervical tumors are lacking. In the present work, we aimed to identify reference genes for RT-qPCR studies of hypoxia in squamous cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia in cervical cancer, i.e. genes regulated by hypoxia in eight cervical cancer cell lines or correlating with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients, were excluded. Among the 182 genes, nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6) that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, were selected for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the optimal set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix) and clinical parameters. The suitability of the three reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalization, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (P<0.001, n = 74) and ABrix (P<0.05, n = 32), and the STC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in squamous cervical cancer samples by RT-qPCR. Moreover, STC2 is a promising prognostic hypoxia biomarker in cervical cancer.

Li Z, Chen Y, Wang X, et al.
LASP-1 induces proliferation, metastasis and cell cycle arrest at the G2/M phase in gallbladder cancer by down-regulating S100P via the PI3K/AKT pathway.
Cancer Lett. 2016; 372(2):239-50 [PubMed] Related Publications
LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.

Zhang H, Li Z, Chu B, et al.
Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma.
Tumour Biol. 2016; 37(6):8305-15 [PubMed] Related Publications
LIM and SH3 protein 1 (LASP-1) is demonstrated to play a key role in occurrence and development of tumors. However, the expression and function of LASP-1 in cholangiocarcinoma (CCA) remain largely unexplored. This study aimed to investigate the effect of regulated LASP-1 expression on migration, invasion, proliferation, and apoptosis of CCA cells and on tumorigenesis in vivo, and to examine clinico-oncological correlates of LASP-1 expression. Expression of LASP-1 by immunohistochemistry was evaluated in CCA tissue samples. HCCC-9810 and RBE cells were transfected with the LASP-1 small interfering RNA (siRNA), and the effect of knocking down LASP-1 gene expression on cell migration, invasion, proliferation, and apoptosis were examined by wound healing, transwell assays, CCK-8 assays, colony formation, and flow cytometry assays, respectively. Xenograft tumor model was used to validate the effect of downregulated LASP-1 in vivo. Our results demonstrated that LASP-1 was over-expressed in CCA tissues, positively correlating with larger tumors, poor histological differentiation, lymph node metastasis, advanced TNM stage, and poor prognosis in CCA patients (P < 0.05). Downregulation of LASP-1 in HCCC-9810 and RBE cell lines significantly increased cell apoptosis and suppressed cell migration, invasion, and proliferation in vitro and tumorigenesis in vivo. Our results indicate that LASP-1 may essentially involve in the metastasis and growth of CCA and clinical significance of LASP-1 may reside in function as a biomarker to predict prognosis and as a promising therapeutic strategy for CCA patients by the inhibition of LASP-1 expression.

Zheng J, Wang F, Lu S, Wang X
LASP-1, regulated by miR-203, promotes tumor proliferation and aggressiveness in human non-small cell lung cancer.
Exp Mol Pathol. 2016; 100(1):116-24 [PubMed] Related Publications
The LIM and SH3 protein 1 (LASP-1) has been reported to be associated with tumor development and progression. However, the expression and potential function of LASP-1 in human non-small cell lung cancer (NSCLC) remains undefined. Thus, this study aims to determine the relationship of LASP-1 expression with the progression and prognosis of NSCLC. Expression of LASP-1 was evaluated in NSCLC tissues and cell lines by real-time PCR, immunohistochemistry and Western blot analysis. The relationship between LASP-1 expression and clinicopathological characteristics was analyzed. The effects of LASP-1 on cell proliferation, migration and invasion were investigated in NSCLC cell lines in vitro and in vivo. Luciferase assay was used to determine whether LASP-1 could be regulated by miR-203. We found that LASP-1 was overexpressed in NSCLC and its expression level was closely correlated with tumor size, advanced TNM stage, lymph node metastasis as well as survival time and could be recognized as an independent prognostic factor of patients. LASP-1 could promote proliferation, migration and invasion of NSCLC cells in vitro and in vivo. Moreover, LASP-1 was proved to be a direct target gene for miR-203. Our results suggest that LASP-1, mediated by miR-203, has crucial functions in the proliferation, migration and invasion of NSCLC.

Du YY, Zhao LM, Chen L, et al.
The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma.
J Gastroenterol Hepatol. 2016; 31(2):384-93 [PubMed] Related Publications
OBJECTIVE: This study determined the expression of microRNA-1 in esophageal squamous cell carcinoma (ESCC) tissue and cell lines to evaluate its effects on clinicopathological parameters and its target genes LASP1 and TAGLN2.
METHODS: The expression of miR-1, lasp1, and tagln2 was detected in 55 ESCC tissues and adjacent normal tissues by reverse transcription-polymerase chain reaction (RT-PCR). The association between miR-1, lasp1, and tagln2 expression and clinicopathological characteristics was observed. MicroRNA-1 (mimics-miR-1) and its inhibitor (Inhibitor-miR-1) were transfected into esophageal cancer cells KYSE 510 and Eca 109; cell proliferation, migration, and invasion assays were carried out. Plasmid construction and dual-luciferase reporter assay were also carried out to indicate whether LASP1 and TAGLN2 were miR-1 target genes. The expression of LASP1 and TAGLN2 was detected with Western blot methods in cell lines, by immunohistochemistry in ESCC tissue.
RESULTS: The gene expression level of microRNA-1 in cancer tissues was significantly lower than that in adjacent normal tissues (P < 0.01). The expression of miR-1 in ESCC was correlated with involvement of lymph nodes (P = 0.002), histologic classification (P = 0.000), and vessel invasion (P = 0.022). The expression of lasp1 and tagln2 increased in cancer tissues compared with in adjacent normal tissues (P < 0.05). MiR-1 suppresses the cell growth, migration, and invasion in vitro. The expression of LASP1 and TAGLN2 decreased in mimics-miR-1 transfected cells, and increased in inhibitor-miR-1 transfected cells. Luciferase reporter assay confirmed that LASP1 and TAGLN2 mRNA actually had the target sites of miR-1.
CONCLUSIONS: miR-1 suppresses cell proliferation, invasiveness, metastasis, and progression of ESCC by binding its targeted genes LASP1 and TAGLN2.

Segerer SE, Bartmann C, Kaspar S, et al.
The cytoskeletal protein LASP-1 differentially regulates migratory activities of choriocarcinoma cells.
Arch Gynecol Obstet. 2016; 293(2):407-14 [PubMed] Related Publications
PURPOSE: During healthy pregnancy, a distinct but limited invasion of trophoblast cells into the uterus occurs. In contrast, excessive trophoblast invasion is associated with placental choriocarcinoma (CC). Overexpression of the cytoskeletal protein LASP-1 was shown to contribute to cancer aggressiveness. Here, the yet unknown role of LASP-1 in CC cells is analysed.
METHODS: Expression of LASP-1 in human primary carcinoma was assessed by immunohistochemistry and confirmed in CC-derived cell lines by immunocytochemistry, RT-PCR and Western blot. After down-regulation of LASP-1 expression with specific si-RNA in CC-derived cell lines, migratory and proliferative activities were analysed by matrigel migration assay and WST-8 test.
RESULTS: LASP-1 expression was detected in human primary choriocarcinoma and in JEG-3, JAR and BeWo cells. Knock down of LASP-1 resulted in a decreased expression of LASP-1 protein in JEG-3 and JAR cells accompanied by a diminished migration and a decreased proliferative activity of these two cell lines. Knockdown of LASP-1 in BeWo cells failed. In consequence, migratory function and proliferation was unaffected.
CONCLUSION: This is the first study describing LASP-1 expression in CC cells. Detecting an affection of migratory processes after LASP-1 silencing, we propose that LASP-1 could impact on metastasis of CC cells.

Vaman V S A, Poppe H, Houben R, et al.
LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression.
PLoS One. 2015; 10(6):e0129219 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.

Kang G, Yun H, Sun CH, et al.
Integrated genomic analyses identify frequent gene fusion events and VHL inactivation in gastrointestinal stromal tumors.
Oncotarget. 2016; 7(6):6538-51 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two genomes of GISTs for integrated analyses. We detected 306 somatic variants in nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome sequencing revealed 328 gene fusions, and the most frequently involved fusion events were associated with IGF2 fused to several partner genes including CCND1, FUS, and LASP1. We additionally identified three recurrent read-through fusion transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found intragenic deletions in one of three exons of the VHL gene and increased mRNAs of VEGF, PDGF-β, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link between VHL inactivation and overexpression of hypoxia-inducible factor target genes in the absence of hypoxia. We also identified copy number gain and increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy number and gene expression results to the KEGG pathways revealed activation of the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type GISTs. These observations will allow us to determine the genetic basis of GISTs and will facilitate further investigation to develop new therapeutic options.

Duvall-Noelle N, Karwandyar A, Richmond A, Raman D
LASP-1: a nuclear hub for the UHRF1-DNMT1-G9a-Snail1 complex.
Oncogene. 2016; 35(9):1122-33 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Nuclear LASP-1 (LIM and SH3 protein-1) has a direct correlation with overall survival of breast cancer patients. In this study, immunohistochemical analysis of a human breast TMA showed that LASP-1 is absent in normal human breast epithelium but the expression increases with malignancy and is highly nuclear in aggressive breast cancer. We investigated whether the chemokines and growth factors present in the tumor microenvironment could trigger nuclear translocation of LASP-1.Treatment of human breast cancer cells with CXCL12, EGF and HRG, and HMEC-CXCR2 cells with CXCL8 facilitated nuclear shuttling of LASP-1. Data from the biochemical analysis of the nuclear and cytosolic fractions further confirmed the nuclear translocation of LASP-1 upon chemokine and growth factor treatment. CXCL12-dependent nuclear import of LASP-1 could be blocked by CXCR4 antagonist, AMD-3100. Knock down of LASP-1 resulted in alterations in gene expression leading to an increased level of cell-junction and extracellular matrix proteins and an altered cytokine secretory profile. Three-dimensional cultures of human breast cancer cells on Matrigel revealed an altered colony growth, morphology and arborization pattern in LASP-1 knockdown cells. Functional analysis of the LASP-1 knockdown cells revealed increased adhesion to collagen IV and decreased invasion through the Matrigel. Proteomic analysis of immunoprecipitates of LASP-1 and subsequent validation approaches revealed that LASP-1 associated with the epigenetic machinery especially UHRF1, DNMT1, G9a and the transcription factor Snail1. Interestingly, LASP-1 associated with UHRF1, G9a, Snail1 and di- and tri-methylated histoneH3 in a CXCL12-dependent manner based on immunoprecipitation and proximity ligation assays. LASP-1 also directly bound to Snail1 which may stabilize Snail1. Thus, nuclear LASP-1 appears to functionally serve as a hub for the epigenetic machinery.

Salvi A, Bongarzone I, Ferrari L, et al.
Molecular characterization of LASP-1 expression reveals vimentin as its new partner in human hepatocellular carcinoma cells.
Int J Oncol. 2015; 46(5):1901-12 [PubMed] Article available free on PMC after 01/10/2019 Related Publications
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We have previously reported that LASP-1 is a downstream protein of the urokinase type plasminogen activator (uPA). Here we investigated the role of LASP-1 in HCC by a molecular and biological characterization of LASP-1 expression in human HCC specimens and in cultured HCC cells. We determined the LASP-1 mRNA expression levels in 55 HCC cases with different hepatic background disease. We identified 3 groups of patients with high, equal or low LASP-1 mRNA levels in HCC tissues compared to the peritumoral (PT) tissues. In particular we found that i) the HCCs displayed a higher LASP-1 mRNA level in HCC compared to PT tissues; ii) the expression levels of LASP-1 mRNA in female HCCs were significantly higher compared to male HCCs; iii) the cirrhotic HCCs displayed a higher LASP-1 mRNA. Further, the biological characterization of the ectopic LASP-1 overexpression in HCC cells, using MALDI-TOF mass spectrometer on the LASP-1 co-immunoprecipitated fractions, displayed vimentin as a novel putative partner of LASP-1. Our results suggest that LASP-1 mRNA overexpression may be mainly implicated in female HCCs and cirrhotic HCCs; and that LASP1 may play its role with vimentin in HCC cells.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. LASP1, Cancer Genetics Web: http://www.cancer-genetics.org/LASP1.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 30 August, 2019     Cancer Genetics Web, Established 1999