TGFβ1 induces endometrial cancer cell adhesion and migration by up-regulating integrin αvβ3 via SMAD-independent MEK-ERK1/2 signaling

被引:18
|
作者
Xiong, Siyuan [1 ]
Klausen, Christian [1 ]
Cheng, Jung-Chien [1 ]
Leung, Peter C. K. [1 ]
机构
[1] Univ British Columbia, BC Childrens Hosp Res Inst, Dept Obstet & Gynaecol, Room 317,950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada
基金
加拿大健康研究院;
关键词
TGF beta 1; Integrin beta 3; Integrin alpha v; Serous endometrial cancer; Type II endometrial cancer; Vitronectin; ALPHA-V-INTEGRIN; TGF-BETA; MONOCLONAL-ANTIBODY; GROWTH-FACTOR; PHASE-I; EXPRESSION; CARCINOMA; PROMOTER; ACTIVATION; GENE;
D O I
10.1016/j.cellsig.2017.03.010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Endometrial cancer is the most common, and second most lethal, gynecological malignancy, and its rates of incidence and death are growing. This is likely attributable to increased numbers of high-risk type II endometrial cancers which account for similar to 30% of cases but similar to 75% of deaths due to their aggressive and metastatic behaviour. Histopathological and in vitro functional studies suggest that aberrant TGF beta 1 signaling may contribute to endometrial cancer development and the acquisition of invasive/metastatic characteristics. However, little is known about the cellular and molecular mechanisms of TGF beta 1 in high-risk endometrial cancers. In the present study, we examined the roles and mechanisms of TGF beta 1 on cell adhesion and motility in type II endometrial cancer cell lines, KLE and HEC-1B. We show that treatment with TGF beta 1 increases cell adhesion to vitronectin and transwell cell migration. We also demonstrate that TGF beta 1 treatment increases integrin beta 3 and alpha v mRNA and protein levels via SMAD-independent MEK-ERK1/2 signaling. Importantly, siRNA depletion or antibody mediated blocking of integrin alpha v beta 3 reversed the effects of TGF beta 1 on cell adhesion and migration. Our results suggest that TGF beta 1-MEK-ERK1/2-integrin alpha v beta 3 signaling could-contribute to the invasive behaviour of high-risk endometrial cancer by promoting cell adhesion and migration.
引用
收藏
页码:92 / 101
页数:10
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