Gene Summary

Gene:SPRR1A; small proline rich protein 1A
Aliases: SPRK
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (9)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 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.

  • Cell Differentiation
  • Genome-Wide Association Study
  • Transcriptome
  • RAD51AP1 protein, human
  • Chromosome 1
  • SPRR1B
  • Squamous Cell Carcinoma
  • Polymerase Chain Reaction
  • Immunohistochemistry
  • Triple Negative Breast Cancer
  • Parathyroid Hormone-Related Protein
  • Ovarian Cancer
  • Neoplastic Cell Transformation
  • Oligonucleotide Array Sequence Analysis
  • Skin Cancer
  • Tissue Array Analysis
  • Messenger RNA
  • Esophageal Cancer
  • Estrogen Receptor alpha
  • Adenocarcinoma
  • Transcription Factors
  • LIM-Homeodomain Proteins
  • Caveolin 1
  • Desmoglein 1
  • Lymphatic Metastasis
  • Rnpc2 protein, mouse
  • Precancerous Conditions
  • MSX2 protein
  • China
  • Trans-Activators
  • Lung Cancer
  • SPRR2E protein, human
  • Immunoenzyme Techniques
  • Receptors, Progesterone
  • Cancer Gene Expression Regulation
  • Gene Regulatory Networks
  • Knockout Mice
  • Biomarkers, Tumor
  • Adenocarcinoma of Lung
  • Cornified Envelope Proline-Rich Proteins
  • Gene Expression Profiling
Tag cloud generated 01 September, 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: SPRR1A (cancer-related)

Wang LX, Li Y, Chen GZ
Network-based co-expression analysis for exploring the potential diagnostic biomarkers of metastatic melanoma.
PLoS One. 2018; 13(1):e0190447 [PubMed] Free Access to Full Article Related Publications
Metastatic melanoma is an aggressive skin cancer and is one of the global malignancies with high mortality and morbidity. It is essential to identify and verify diagnostic biomarkers of early metastatic melanoma. Previous studies have systematically assessed protein biomarkers and mRNA-based expression characteristics. However, molecular markers for the early diagnosis of metastatic melanoma have not been identified. To explore potential regulatory targets, we have analyzed the gene microarray expression profiles of malignant melanoma samples by co-expression analysis based on the network approach. The differentially expressed genes (DEGs) were screened by the EdgeR package of R software. A weighted gene co-expression network analysis (WGCNA) was used for the identification of DEGs in the special gene modules and hub genes. Subsequently, a protein-protein interaction network was constructed to extract hub genes associated with gene modules. Finally, twenty-four important hub genes (RASGRP2, IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A, KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were treated as valuable factors involved in the immune response and tumor cell development in tumorigenesis. In addition, a transcriptional regulatory network was constructed for these specific modules or hub genes, and a few core transcriptional regulators were found to be mostly associated with our hub genes, including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our understanding of the biological process of malignant melanoma metastasis, enabling us to identify specific genes to use for diagnostic and prognostic markers and possibly for targeted therapy.

Chudasama D, Bo V, Hall M, et al.
Identification of cancer biomarkers of prognostic value using specific gene regulatory networks (GRN): a novel role of RAD51AP1 for ovarian and lung cancers.
Carcinogenesis. 2018; 39(3):407-417 [PubMed] Free Access to Full Article Related Publications
To date, microarray analyses have led to the discovery of numerous individual 'molecular signatures' associated with specific cancers. However, there are serious limitations for the adoption of these multi-gene signatures in the clinical environment for diagnostic or prognostic testing as studies with more power need to be carried out. This may involve larger richer cohorts and more advanced analyses. In this study, we conduct analyses-based on gene regulatory network-to reveal distinct and common biomarkers across cancer types. Using microarray data of triple-negative and medullary breast, ovarian and lung cancers applied to a combination of glasso and Bayesian networks (BNs), we derived a unique network-containing genes that are uniquely involved: small proline-rich protein 1A (SPRR1A), follistatin like 1 (FSTL1), collagen type XII alpha 1 (COL12A1) and RAD51 associated protein 1 (RAD51AP1). RAD51AP1 and FSTL1 are significantly overexpressed in ovarian cancer patients but only RAD51AP1 is upregulated in lung cancer patients compared with healthy controls. The upregulation of RAD51AP1 was mirrored in the bloods of both ovarian and lung cancer patients, and Kaplan-Meier (KM) plots predicted poorer overall survival (OS) in patients with high expression of RAD51AP1. Suppression of RAD51AP1 by RNA interference reduced cell proliferation in vitro in ovarian (SKOV3) and lung (A549) cancer cells. This effect appears to be modulated by a decrease in the expression of mTOR-related genes and pro-metastatic candidate genes. Our data describe how an initial in silico approach can generate novel biomarkers that could potentially support current clinical practice and improve long-term outcomes.

Chen G, Li G, Luo M, et al.
Clinical significance of SPRR1A expression in progesterone receptor-positive breast cancer.
Tumour Biol. 2015; 36(4):2601-5 [PubMed] Related Publications
Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8%), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression (P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status (P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression (P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive (P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression (P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups.

Heikinheimo K, Kurppa KJ, Laiho A, et al.
Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor.
J Dent Res. 2015; 94(1):101-11 [PubMed] Related Publications
The aim of the study was to characterize the molecular relationship between ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide expression analysis. Total RNA from 27 fresh tumor samples of 15 solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was hybridized on Affymetrix whole genome arrays. Hierarchical clustering separated ameloblastomas and KCOTs into 2 distinct groups. The gene set enrichment analysis based on 303 dental genes showed a similar separation of ameloblastomas and KCOTs. Early dental epithelial markers PITX2, MSX2, DLX2, RUNX1, and ISL1 were differentially overexpressed in ameloblastoma, indicating its dental identity. Also, PTHLH, a hormone involved in tooth eruption and invasive growth, was one of the most differentially upregulated genes in ameloblastoma. The most differentially overexpressed genes in KCOT were squamous epithelial differentiation markers SPRR1A, KRTDAP, and KRT4, as well as DSG1, a component of desmosomal cell-cell junctions. Additonally, the epithelial stem cell marker SOX2 was significantly upregulated in KCOT when compared with ameloblastoma. Taken together, the gene expression profile of ameloblastoma reflects differentiation from dental lamina toward the cap/bell stage of tooth development, as indicated by dental epithelium-specific transcription factors. In contrast, gene expression of KCOT indicates differentiation toward keratinocytes.

Zhang H, Gao J, Zhao Z, et al.
Clinical implications of SPRR1A expression in diffuse large B-cell lymphomas: a prospective, observational study.
BMC Cancer. 2014; 14:333 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Certain markers have been identified over the last 10 years that facilitate the prediction of a patient's prognosis; these markers have been proposed to be useful for risk stratification of lymphoma patients and for the development of specific therapeutic strategies. In the present study, we assessed the potential prognostic value of SPRR1A expression in 967 patients with diffuse large B-cell lymphomas.
METHODS: All patients were enrolled between 2001 and 2007 (median follow-up, 53.3 months) in the Second Hospital of Dalian Medical University, First Hospital of China Medical University, and Liaoning Cancer Hospital. Immunohistochemical analysis was used to evaluate the expression of SPRR1A. Survival was analyzed using the Kaplan-Meier method. Multivariate analysis was conducted to adjust the effect of SPRR1A expression for potential, well-known, independent prognostic factors.
RESULTS: Of the 967 patients examined, SPRR1A expression was detected in 305 (31.54%) patients on immunohistochemical analysis. The 5-year survival rate was significantly lower in patients with SPRR1A expression than in those without (26.9% vs. 53.2%, P < 0.001). Multivariate analysis identified SPRR1A expression as an independent predictor of survival in addition to lactate dehydrogenase level, clinical stage, and histologic subtype.
CONCLUSIONS: SPRR1A expression may be useful as a prognostic factor for diffuse large B-cell lymphoma.

Leclerc D, Lévesque N, Cao Y, et al.
Genes with aberrant expression in murine preneoplastic intestine show epigenetic and expression changes in normal mucosa of colon cancer patients.
Cancer Prev Res (Phila). 2013; 6(11):1171-81 [PubMed] Related Publications
An understanding of early genetic/epigenetic changes in colorectal cancer would aid in diagnosis and prognosis. To identify these changes in human preneoplastic tissue, we first studied our mouse model in which Mthfr⁺/⁻ BALB/c mice fed folate-deficient diets develop intestinal tumors in contrast to Mthfr⁺/⁺ BALB/c mice fed control diets. Transcriptome profiling was performed in normal intestine from mice with low or high tumor susceptibility. We identified 12 upregulated and 51 downregulated genes in tumor-prone mice. Affected pathways included retinoid acid synthesis, lipid and glucose metabolism, apoptosis and inflammation. We compared murine candidates from this microarray analysis, and murine candidates from an earlier strain-based comparison, with a set of human genes that we had identified in previous methylome profiling of normal human colonic mucosa, from colorectal cancer patients and controls. From the extensive list of human methylome candidates, our approach uncovered five orthologous genes that had shown changes in murine expression profiles (PDK4, SPRR1A, SPRR2A, NR1H4, and PYCARD). The human orthologs were assayed by bisulfite-pyrosequencing for methylation at 14 CpGs. All CpGs exhibited significant methylation differences in normal mucosa between colorectal cancer patients and controls; expression differences for these genes were also observed. PYCARD and NR1H4 methylation differences showed promise as markers for presence of polyps in controls. We conclude that common pathways are disturbed in preneoplastic intestine in our animal model and morphologically normal mucosa of patients with colorectal cancer, and present an initial version of a DNA methylation-based signature for human preneoplastic colon.

Mercier I, Casimiro MC, Zhou J, et al.
Genetic ablation of caveolin-1 drives estrogen-hypersensitivity and the development of DCIS-like mammary lesions.
Am J Pathol. 2009; 174(4):1172-90 [PubMed] Free Access to Full Article Related Publications
Caveolin-1 (Cav-1) loss-of-function mutations are exclusively associated with estrogen receptor-positive (ER(+)) human breast cancers. To dissect the role of Cav-1 loss-of-function in the pathogenesis of human breast cancers, we used Cav-1(-/-) null mice as a model system. First, we demonstrated that Cav-1(-/-) mammary epithelia overexpress two well-established ER co-activator genes, CAPER and Foxa1, in addition to ER-alpha. Thus, the functional loss of Cav-1 may be sufficient to confer estrogen-hypersensitivity in the mammary gland. To test this hypothesis directly, we subjected Cav-1(-/-) mice to ovariectomy and estrogen supplementation. As predicted, Cav-1(-/-) mammary glands were hyper-responsive to estrogen and developed dysplastic mammary lesions with adjacent stromal angiogenesis that resemble human ductal carcinoma in situ. Based on an extensive biomarker analysis, these Cav-1(-/-) mammary lesions contain cells that are hyperproliferative and stain positively with nucleolar (B23/nucleophosmin) and stem/progenitor cell markers (SPRR1A and beta-catenin). Genome-wide transcriptional profiling identified many estrogen-related genes that were over-expressed in Cav-1(-/-) mammary glands, including CAPER--an ER co-activator gene and putative stem/progenitor cell marker. Analysis of human breast cancer samples revealed that CAPER is overexpressed and undergoes a cytoplasmic-to-nuclear shift during the transition from pre-malignancy to ductal carcinoma in situ. Thus, Cav-1(-/-) null mice are a new preclinical model for studying the molecular paradigm of estrogen hypersensitivity and the development of estrogen-dependent ductal carcinoma in situ lesions.

Kim KY, Kim BC, Xu Z, Kim SJ
Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells.
J Biol Chem. 2004; 279(28):29478-84 [PubMed] Related Publications
Although transforming growth factor beta1 (TGF-beta1) acts via the Smad signaling pathway to initiate de novo gene transcription, the TGF-beta1-induced MAPK kinase activation that is involved in the regulation of apoptosis is less well understood. Even though the p38 MAP kinase and c-Jun NH(2)-terminal kinases (JNKs) are involved in TGF-beta1-induced cell death in hepatoma cells, the upstream mediators of these kinases remain to be defined. We show here that the members of the mixed lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper-bearing kinase (DLK)) are expressed in FaO rat hepatoma cells and are likely to act between p38 and TGF-beta receptor kinase in death signaling. TGF-beta1 treatment leads to an increase in MLK3 activity. Overexpression of MLK3 enhances TGF-beta1-induced apoptotic death in FaO cells and Hep3B human hepatoma cells, whereas expression of the dominant-negative forms of MLK3 suppresses cell death induced by TGF-beta1. The dominant-negative forms of MLK1 and -2 also suppress TGF-beta1-induced cell death. In MLK3-overexpressing cells, ERK, JNKs, and p38 MAP kinases were further activated in response to TGF-beta1 compared with the control cells. In contrast, overexpression of the dominant-negative MLK3 resulted in suppression of TGF-beta1-induced MAP kinase activation and TGF-beta1-induced caspase-3 activation. We also show that only the inhibition of the p38 pathway suppressed TGF-beta1-induced apoptosis. These observations support a role for MLKs in the TGF-beta1-induced cell death mechanism.

Luo A, Kong J, Hu G, et al.
Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray.
Oncogene. 2004; 23(6):1291-9 [PubMed] Related Publications
To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.

Hippo Y, Yashiro M, Ishii M, et al.
Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes.
Cancer Res. 2001; 61(3):889-95 [PubMed] Related Publications
Scirrhous gastric cancer is often accompanied by metastasis to the peritoneum and/or lymph nodes, resulting in the highest mortality rate among gastric cancers. Mechanisms involved in gastric cancer metastasis are not fully clarified because metastasis involves multiple steps and requires the accumulation of altered expression of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer metastasis. In this study, we performed global analysis on differential gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its derivative sublines with high potential for metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes (OCUM-2MLN) in a nude mice model. By applying a high-density oligonucleotide array method, expression of approximately 6800 genes was analyzed, and selected genes were confirmed by the Northern blot method. In our observations in OCUM-2MD3 cells, 12 genes were up-regulated, and 20 genes were down-regulated. In OCUM-2MLN cells, five genes were up-regulated, and five genes were down-regulated. The analysis revealed two functional gene clusters with altered expression: (a) down-regulation of a cluster of squamous cell differentiation marker genes such as small proline-rich proteins [SPRRs (SPRR1A, SPRR1B, and SPRR2A], annexin A1, epithelial membrane protein 1, cellular retinoic acid-binding protein 2, and mesothelin in OCUM-2MD3 cells; and (b) up-regulation of a cluster of antigen-presenting genes such as MHC class II (DP, DR, and DM) and invariant chain (II) in OCUM-2MLN cells through up-regulation of CIITA (MHC class II transactivator). We then analyzed six gastric cancer cell lines by Northern blot and observed preferential up-regulation of trefoil factor 1, alpha-1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells prone to peritoneal dissemination. Genes highly correlated with invasion or peritoneal dissemination of gastric cancer, such as E-cadherin or integrin beta4, were down-regulated in both of the derivative cell lines analyzed in this study. This is the first demonstration of global gene expression analysis of gastric cancer cells with different metastatic potentials, and these results provide a new insight in the study of human gastric cancer metastasis.

Robinson PA, Marley JJ, High AS, Hume WJ
Differential expression of protease inhibitor and small proline-rich protein genes between normal human oral tissue and odontogenic keratocysts.
Arch Oral Biol. 1994; 39(3):251-9 [PubMed] Related Publications
The technique of differential hybridization was used to compare gene transcription between normal oral mucosa and odontogenic keratocyst lining. Protease inhibitors, elafin and stefin-B as well as beta-actin and two epithelial-specific small proline-rich (spr) proteins, which we have named SPRC and SPRK and which are distinct from salivary proline-rich proteins, were differentially expressed. Increased abundance of alpha I(I) collagen and elafin transcripts was demonstrated in the keratocyst, with decreased abundance of stefin B, SPRC and cytokeratins 4 and 13 transcripts compared to normal palatal mucosa. The deduced protein sequences of SPRC and SPRK were described and compared, and the relative abundance of their respective cDNAs in palatal and keratocyst libraries determined. Identification of factors controlling transcription of these genes could advance our understanding of the development of odontogenic keratocysts.

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Cite this page: Cotterill SJ. SPRR1A, Cancer Genetics Web: http://www.cancer-genetics.org/SPRR1A.htm Accessed:

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