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

Oncogene volume 34, pages 373–383 (2015)Cite this article

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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.

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Acknowledgements

The authors thank Dr Michelle Hirsch for critical review of the manuscript, Laura Selfors of biocomputing analyzes of the RPPA data, and members of the Drapkin laboratory for fruitful discussions. This work was supported by the NIH/NCI SPORE in OC P50-CA105009 (RD), U01 CA-152990 (RD), R21 CA-156021 (RD); NIH/NINDS P01 NS047572 (JM), the Honorable Tina Brozman ‘Tina’s Wish’ Foundation (JM, RD), the Dr Miriam and Sheldon G. Adelson Medical Research Foundation (GBM and RD), The Robert and Debra First Fund (RD), The Gamel Family Fund (RD), the Ovarian Cancer Research Fund (RD), The Madeline Franchi Ovations for the Cure Fund (AC), the Mary Kay Foundation (RD), the Sandy Rollman Ovarian Cancer Foundation (RD), the Dana-Farber Cancer Institute (DFCI) Strategic Initiative (JM), the Executive Council of the Susan Smith Center for Women’s Cancers at the DFCI, the Triple Negative Breast Cancer Foundation (SG), and the New Jersey Commission on Cancer Research (SG). SILG is a recipient of grants from Arthur Sachs/Fulbright/Harvard, La Fondation Philippe and La Fondation de France—‘Recherche clinique en cancérologie – Aide à la mobilité des chercheurs’.

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Author notes

  1. S I Labidi-Galy and A Clauss: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    S I Labidi-Galy, A Clauss, V Ng, S Duraisamy, K M Elias, H-Y Piao, G Badalian-Very & R Drapkin

  2. Harvard Medical School, Boston, MA, USA

    S I Labidi-Galy, A Clauss, S Duraisamy, K M Elias, G Badalian-Very, U-B Kang, S Ficarro, J A Marto & R Drapkin

  3. Division of Gynecologic Oncology, Brigham and Women’s Hospital, Boston, MA, USA

    K M Elias

  4. The Cancer Institute of New Jersey, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    E Bilal & S Ganesan

  5. Department of Cell Biology, Harvard Medical School, Boston, MA, USA

    R A Davidowitz

  6. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Y Lu & G B Mills

  7. Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary

    B Györffy

  8. Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA, USA

    U-B Kang, S Ficarro & J A Marto

  9. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    R Drapkin

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  1. S I Labidi-Galy
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Labidi-Galy, S., Clauss, A., Ng, V. et al. Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors. Oncogene 34, 373–383 (2015). https://doi.org/10.1038/onc.2013.562

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