AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer

Laura M. Divine, Mai R. Nguyen, Eric Meller, Riva A. Desai, Batool Arif, Erinn B. Rankin, Katherine H. Bligard, Cherise Meyerson, Ian S. Hagemann, Maria Massad, Premal H. Thaker, Andrea R. Hagemann, Carolyn K. McCourt, Matt A. Powell, David G. Mutch, Katherine C. Fuh

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer.

Original languageEnglish
Pages (from-to)77291-77305
Number of pages15
JournalOncotarget
Volume7
Issue number47
DOIs
StatePublished - 2016

Keywords

  • ARK1
  • AXL
  • Endometrial cancer
  • MMP
  • UPA

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