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

被引：28

作者：

Divine, Laura M. ^{[1
]}

Nguyen, Mai R. ^{[1
]}

Meller, Eric ^{[1
]}

Desai, Riva A. ^{[1
]}

Arif, Batool ^{[1
]}

Rankin, Erinn B. ^{[2
,3
]}

Bligard, Katherine H. ^{[1
]}

Meyerson, Cherise ^{[4
]}

Hagemann, Ian S. ^{[1
,4
]}

Massad, Maria ^{[1
]}

Thaker, Premal H. ^{[1
]}

Hagemann, Andrea R. ^{[1
]}

McCourt, Carolyn K. ^{[1
]}

Powell, Matt A. ^{[1
]}

Mutch, David G. ^{[1
]}

Fuh, Katherine C. ^{[1
,5
]}

机构：

[1] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA

[2] Stanford Univ, Med Ctr, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA

[3] Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Stanford, CA 94305 USA

[4] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA

[5] Washington Univ, Ctr Reprod Hlth Sci CRepHS, St Louis, MO 63130 USA

来源：

ONCOTARGET | 2016年 / 7卷 / 47期

关键词：

AXL; endometrial cancer; uPA; MMP; ARK1; RECEPTOR TYROSINE KINASE; TO-MESENCHYMAL TRANSITION; BREAST-CANCER; THERAPEUTIC TARGET; PLASMINOGEN-ACTIVATOR; TUMOR INVASION; GROWTH; RESISTANCE; INHIBITOR; GAS6/AXL;

D O I：

10.18632/oncotarget.12637

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：77291 / 77305

页数：15

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