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Low expression of WWC1, a tumor suppressor gene, is associated with aggressive breast cancer and poor survival outcome.

08:00 EDT 18th May 2019 | BioPortfolio

Summary of "Low expression of WWC1, a tumor suppressor gene, is associated with aggressive breast cancer and poor survival outcome."

The WW and C2 domain containing 1 gene encodes a protein named WWC1 (or KIBRA), which is involved in the Hippo signaling pathway. WWC1 is often lost in triple-negative breast cancer and has been shown to suppress tumor metastasis. In this study, 470 breast cancer patients were recruited and WWC1 expression in the tumor samples were measured with quantitative reverse transcriptase-PCR (qRT-PCR). Associations of WWC1 expression with breast cancer survival were analyzed using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. The relationship between WWC1 expression and methylation was evaluated in a dataset from The Cancer Genome Atlas (TCGA). Using our microarray data on gene expression and the Ingenuity Pathway Analysis, we predicted the WWC1-associated signaling pathways in breast cancer. Our results showed that low expression of WWC1 was significantly associated with advanced stage diseases, high-grade tumors, and ER- or PR-negative status. Compared to those with high expression, patients with low WWC1 had higher risk of breast cancer relapse [hazard ratio (HR) = 2.06, 95% confidence interval (CI): 1.26-3.37] and higher risk of death (HR=2.76, 95%
CI:
1.51-5.03). The association with relapse-free survival remained significant after adjustment for disease stage, tumor grade and hormone receptor status, and was replicated in a public dataset. Analysis of high-throughput gene expression data indicated that WWC1 was involved in the Hippo signaling pathway. Online data also suggested that DNA methylation was inversely associated with WWC1 expression. The study confirmed that low WWC1 expression was associated with aggressive breast cancer and poor survival outcomes.

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Name: FEBS open bio
ISSN: 2211-5463
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Medical and Biotech [MESH] Definitions

A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions.

A nuclear protein and tumor suppressor that contains a C-terminal PHD ZINC FINGER. It is expressed in different isoforms in various tissues and interacts with TUMOR SUPPRESSOR PROTEIN P53 to negatively regulate cell growth. Reduced expression and chromosomal rearrangements of the ING1 gene are associated with different cancers including HEAD AND NECK NEOPLASMS.

A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.

A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 17 at locus 17q21. Mutations of this gene are associated with the formation of familial breast and ovarian cancer. It encodes a large, nuclear protein that is a component of DNA repair pathways.

Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.

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