Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors

S. I. Labidi-Galy, A. Clauss, V. Ng, S. Duraisamy, K. M. Elias, H. Y. Piao, E. Bilal, R. A. Davidowitz, Y. Lu, G. Badalian-Very, B. Györffy, U. B. Kang, S. Ficarro, S. Ganesan, G. B. Mills, J. A. Marto, R. Drapkin

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.

Original languageEnglish (US)
Pages (from-to)299-309
Number of pages11
JournalOncogene
Volume34
Issue number3
DOIs
StatePublished - Jan 15 2015
Externally publishedYes

Keywords

  • Basal-like breast cancer
  • Elafin
  • MAP kinase
  • Mitogen
  • Ovarian cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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