Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome

Katia Rea, Patrizia Pinciroli, Marialuisa Sensi, Federica Alciato, Brigitte Bisaro, Ludmila Lozneanu, Francesco Raspagliesi, Floriana Centritto, Sara Cabodi, Paola Defilippi, Gian Carlo Avanzi, Silvana Canevari, Antonella Tomassetti

Research output: Contribution to journalArticle

Abstract

High-grade epithelial ovarian cancer (HGEOC) is a clinically diverse and molecularly heterogeneous disease comprising subtypes with distinct biological features and outcomes. The receptor tyrosine kinases, expressed by EOC cells, and their ligands, present in the microenvironment, activate signaling pathways, which promote EOC cells dissemination. Herein, we established a molecular link between the presence of Gas6 ligand in the ascites of HGEOCs, the expression and activation of its receptor Axl in ovarian cancer cell lines and biopsies, and the progression of these tumors. We demonstrated that Gas6/Axl signalling converges on the integrin β3 pathway in the presence of the adaptor protein p130Cas, thus inducing tumor cell adhesion to the extracellular matrix and invasion. Accordingly, Axl and p130Cas were significantly co-expressed in HGEOC samples. Clinically, we identified an Axl-associated signature of 62 genes able to portray the HGEOCs with the shortest overall survival. These data biologically characterize a group of HGEOCs and could help guide a more effective therapeutic approach to be taken for these patients.

Original languageEnglish
Pages (from-to)30859-30875
Number of pages17
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - 2015

Keywords

  • Axl
  • Extracellular matrix
  • Gas6
  • Ovarian cancer
  • P130Cas

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Rea, K., Pinciroli, P., Sensi, M., Alciato, F., Bisaro, B., Lozneanu, L., Raspagliesi, F., Centritto, F., Cabodi, S., Defilippi, P., Avanzi, G. C., Canevari, S., & Tomassetti, A. (2015). Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome. Oncotarget, 6(31), 30859-30875. https://doi.org/10.18632/oncotarget.5087