Divine Laura M, Nguyen Mai R, Meller Eric, Desai Riva A, Arif Batool, Rankin Erinn B, Bligard Katherine H, Meyerson Cherise, Hagemann Ian S, Massad Maria, Thaker Premal H, Hagemann Andrea R, McCourt Carolyn K, Powell Matt A, Mutch David G, Fuh Katherine C
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
Oncotarget. 2016 Nov 22;7(47):77291-77305. doi: 10.18632/oncotarget.12637.
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.
受体酪氨酸激酶AXL可促进迁移、侵袭和转移。在此，我们评估了AXL在子宫内膜癌中的作用。在76%（63/83）的晚期标本和77%（82/107）的高级别标本中发现AXL的高免疫组化表达，且这与子宫浆液性癌患者较差的生存率相关。在体外，AXL的基因沉默抑制了ARK1子宫内膜癌细胞的迁移和侵袭，但对其增殖没有影响。AXL缺陷型细胞显示磷酸化AKT以及尿激酶型纤溶酶原激活剂（uPA）、基质金属蛋白酶（MMP）-1、MMP-2、MMP-3和MMP-9的表达显著降低。在用人AXL缺陷型ARK1细胞建立的人子宫浆液性癌异种移植模型中，肿瘤负荷明显低于用对照ARK1细胞建立的异种移植模型。这些发现共同强调了AXL作为转移性子宫内膜癌治疗候选靶点的治疗潜力。
