Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ.
Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ.
复制标题
葡萄糖通过调节YAP1和TAZ的功能促进膀胱癌上皮间质转化
DOI：
10.1111/jcmm.15653
复制
发表时间：
2020-09
影响因子：
5.3
通讯作者：
Lin Q
中科院分区：
文献类型：
--
作者：
Li S;Zhu H;Chen H;Xia J;Zhang F;Xu R;Lin Q
血糖水平和2型糖尿病(T2D)都与肿瘤的发生和上皮-间充质转化(EMT)有关。EMT促进膀胱癌(BC)的转移发展，但高糖促进BC的EMT的机制尚不清楚。因此，我们试图阐明由于葡萄糖水平升高而促进EMT的机制。T24和UMUC-3细胞在含有不同葡萄糖浓度的培养液中培养。用Western blotting和qPCR分析YAP1、TAZ、GLUT1和EMT相关标志物的表达。用四甲基偶氮唑盐比色法和Transwell法分别检测BC细胞的增殖和侵袭能力。建立糖尿病裸鼠移植瘤模型，观察肿瘤的体内生长和转移情况。T2D与BC的病理分级(P=0.016)和TNM分期(P<0.01)呈正相关。在体外和体内条件下，高糖均可引起BC细胞的增殖和侵袭。高糖还促进了BC细胞的EMTs，并增加了YAP1和TAZ的表达。YAP1或TAZ基因敲除改变了EMT标志物的表达，降低了GLUT1的表达。总体而言，我们的结果表明，高糖水平通过YAP1和TAZ调节促进了BC细胞中的EMT。这些效应分子可能成为治疗合并T2D的BC患者的良好靶点。
Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial‐mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high‐glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC‐3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT‐associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High‐glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high‐glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.
登录
查看更多内容
影响因子：
9.7
作者：
Shen, Shuying;Huang, Kangmao;Ma, Jianjun
通讯作者：
Ma, Jianjun
影响因子：
4
作者：
Sun, Shichao;Sun, Yao;Bai, Lei
通讯作者：
Bai, Lei
影响因子：
5.6
作者：
Wei, Huamei;Wang, Jianchu;Tang, Qianli
通讯作者：
Tang, Qianli
影响因子：
5.4
作者：
Fang, Hong;Yao, Baodong;Zhao, Yanping
通讯作者：
Zhao, Yanping
lncRNA H19通过miR-29b-3p作为竞争性内源RNA调节膀胱癌的上皮间质转化和转移
DOI：
10.1016/j.bbamcr.2017.08.001
发表时间：
2017-10-01
影响因子：
5.1
作者：
Lv, Mengxin;Zhong, Zhenyu;Chen, Junxia
通讯作者：
Chen, Junxia