The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
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DOI：
10.18632/oncotarget.8408
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Kojima T
中科院分区：
文献类型：
--
作者：
Shimada H;Satohisa S;Kohno T;Takahashi S;Hatakeyama T;Konno T;Tsujiwaki M;Saito T;Kojima T
脂解刺激的脂蛋白受体（LSR）已被确定为一种新的分子组成的三细胞接触，具有屏障功能的细胞片层。LSR募集三细胞蛋白（TRIC），这是三细胞紧密连接的第一个分子组分。LSR的敲低增加细胞运动性和某些癌细胞的侵袭。然而，LSR在子宫内膜癌中的行为和作用仍然未知。在本研究中，我们研究了LSR在正常和子宫内膜癌细胞在体内和体外的行为和作用。在子宫内膜异位症和子宫内膜癌中，LSR不仅在根尖下区域观察到，而且在整个侧部区域以及在分泌期的正常子宫内膜上皮细胞中观察到，并且癌中的LSR与恶性程度相关。在子宫内膜癌细胞系Sawano细胞中通过siRNA敲低LSR，诱导细胞迁移、侵袭和增殖，而TRIC从膜上的三细胞区域重新定位到双细胞区域。在Sawano细胞和正常HEE中，观察到瘦素诱导的LSR减少和脂联素以及2型糖尿病药物二甲双胍和黄连素诱导的LSR增加通过不同的信号通路，包括JAK 2/STAT。在Sawano细胞中，二甲双胍和小檗碱阻止了siRNA和瘦素处理下调LSR诱导的细胞迁移和侵袭。探讨肥胖时子宫内膜LSR表达下调的机制对子宫内膜癌的诊断和治疗具有重要意义。
Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel molecular constituent of tricellular contacts that have a barrier function for the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular component of tricellular tight junctions. Knockdown of LSR increases cell motility and invasion of certain cancer cells. However, the behavior and the roles of LSR in endometrial cancer remain unknown. In the present study, we investigated the behavior and roles of LSR in normal and endometrial cancer cells in vivo and in vitro. In endometriosis and endometrial cancer, LSR was observed not only in the subapical region but also throughout the lateral region as well as in normal endometrial epithelial cells in the secretory phase, and LSR in the cancer was reduced in correlation with the malignancy. Knockdown of LSR by the siRNA in cells of the endometrial cancer cell line Sawano, induced cell migration, invasion and proliferation, while TRIC relocalized from the tricellular region to the bicellular region at the membrane. In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT. In Sawano cells, metformin and berberine prevented cell migration and invasion induced by downregulation of LSR by the siRNA and leptin treatment. The dissection of the mechanism in the downregulation of endometrial LSR during obesity is important in developing new diagnostic and therapy for endometrial cancer.
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影响因子：
11.2
作者：
Ho GY;Wang T;Gunter MJ;Strickler HD;Cushman M;Kaplan RC;Wassertheil-Smoller S;Xue X;Rajpathak SN;Chlebowski RT;Vitolins MZ;Scherer PE;Rohan TE
通讯作者：
Rohan TE
DOI：
10.1083/jcb.200510043
发表时间：
2005-12-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ikenouchi J;Furuse M;Furuse K;Sasaki H;Tsukita S;Tsukita S
通讯作者：
Tsukita S
影响因子：
2.3
作者：
Buck, Volker U.;Windoffer, Reinhard;Classen-Linke, Irmgard
通讯作者：
Classen-Linke, Irmgard
影响因子：
2.6
作者：
Anderson, Annie S.;Key, Timothy J.;Romieu, Isabelle
通讯作者：
Romieu, Isabelle
循环脂联素、瘦素和脂联素-瘦素比率与子宫内膜癌风险：来自流行病学研究荟萃分析的证据。
影响因子：
6.4
作者：
Gong, Ting-Ting;Wu, Qi-Jun;Ma, Xiao-Xin
通讯作者：
Ma, Xiao-Xin