BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

David M. Gau, Jamie L. Lesnock, Brian L. Hood, Rohit Bhargava, Mai Sun, Kathleen Darcy, Soumya Luthra, Uma Chandran, Thomas P. Conrads, Robert P. Edwards, Joseph L. Kelley, Thomas C. Krivak, Partha Roy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 BRCA1null 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.

Original languageEnglish
Pages (from-to)1884-1892
Number of pages9
JournalCell Cycle
Volume14
Issue number12
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

Keywords

  • BRCA1
  • Cell Motility
  • Ovarian cancer
  • Profilin-1

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