1. AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer.
- Author
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Divine LM, Nguyen MR, Meller E, Desai RA, Arif B, Rankin EB, Bligard KH, Meyerson C, Hagemann IS, Massad M, Thaker PH, Hagemann AR, McCourt CK, Powell MA, Mutch DG, and Fuh KC
- Subjects
- Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Endometrial Neoplasms genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphorylation, Prognosis, Signal Transduction, Survival Analysis, Up-Regulation, Axl Receptor Tyrosine Kinase, Endometrial Neoplasms metabolism, Endometrial Neoplasms pathology, Extracellular Matrix Proteins metabolism, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Receptor Protein-Tyrosine Kinases genetics, Receptor Protein-Tyrosine Kinases metabolism
- 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.
- Published
- 2016
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