Oncotarget

Research Papers:

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 and Katherine C. Fuh _

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Oncotarget. 2016; 7:77291-77305. https://doi.org/10.18632/oncotarget.12637

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Abstract

Laura M. Divine1,*, Mai R. Nguyen1,*, Eric Meller1, Riva A. Desai1, Batool Arif1, Erinn B. Rankin2,3, Katherine H. Bligard1, Cherise Meyerson4, Ian S. Hagemann1,4, Maria Massad1, Premal H. Thaker1, Andrea R. Hagemann1, Carolyn K. McCourt1, Matt A. Powell1, David G. Mutch1, Katherine C. Fuh1,5

1Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA

2Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA

3Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA, USA

4Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

5Center for Reproductive Health Sciences (CRepHS), Washington University in St. Louis, St. Louis, MO, USA

*These authors have contributed equally to this work

Correspondence to:

Katherine C. Fuh, email: [email protected]

Keywords: AXL, endometrial cancer, uPA, MMP, ARK1

Received: May 12, 2016    Accepted: September 24, 2016    Published: October 13, 2016

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.


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