期刊
CELL CYCLE
卷 14, 期 12, 页码 1884-1892出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1036203
关键词
BRCA1; cell Motility; ovarian cancer; profilin-1; EOC; Epithelial Ovarian Cancer; BRCA1; Breast cancer susceptibility gene 1; BRCA2; Breast cancer susceptibility gene 2; PFN1; Profilin-1; ID1; Inhibitor of differentiation-1; ERM; Ezrin-Radixin-Moesin; CFN1; Cofilin-1; CAPG; Macrophage capping protein; SPTBN1; Non-erythrocytic spectrin Chain-1; PP2A; Protein phosphatase 2A; HYOU1; Hypoxia upregulated protein 1; CAPN1; Calpain-1; FFPE; Formalin-fixed paraffin-embedded; WT; Wild-type; Luc; luciferase; IHC; Immunohistochemistry; LC MS-MS; Liquid chromatography tandem mass spectrometry
类别
资金
- National Institute of Health [2R01-CA108607]
- National Science Foundation Graduate Research Fellowship [2012139050]
- University of Pittsburgh Cancer Institute Cancer Biomarkers Facility [P30-CA047904]
Functional loss of expression of breast cancer susceptibility gene 1(BRCA1) has been implicated in genomic instability and cancer progression. There is emerging evidence that BRCA1 gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1(+/+) and BRCA1(null) status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.
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