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AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer.
- Source :
-
Oncotarget [Oncotarget] 2016 Nov 22; Vol. 7 (47), pp. 77291-77305. - Publication Year :
- 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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27764792
- Full Text :
- https://doi.org/10.18632/oncotarget.12637