T-cadherin通过下调EGFR-PI3K-AKT信号轴抑制膀胱癌的发展

T-cadherin inhibits the development of bladder cancer by downregulating the EGFR-PI3K-AKT signaling axis

目的探究T-钙黏蛋白(T-cadherin,T-cad)在膀胱癌发生发展中的作用及其机制。方法检测膀胱癌患者和对照组人群血清中T-cad mRNA的表达差异;比较T-cad低表达和高表达膀胱癌患者的临床分期和肿瘤组织病理分级差异;建立T-cad过表达EJ1细胞系,通过CCK 8实验、克隆形成实验检测过表达T-cad对EJ1细胞增殖和克隆形成能力的影响;利用Western blot技术分析过表达T-cad对EJ1细胞PI3K-AKT信号的影响。结果与对照组人群相比,膀胱癌患者血清中T-cad mRNA表达水平较低(P<0.001);T-cad低表达膀胱癌病理分级较高(P<0.05);过表达T-cad抑制EJ1细胞的增殖(P<0.0001)和克隆形成(P<0.05)能力;过表达T-cad下调EJ1细胞中EGFR(P<0.01)、PI3Kα(P<0.001)和p-AKT(P<0.001)表达水平。结论T-cad通过下调EGFR-PI3K-AKT信号轴抑制膀胱癌的发展。

Objective To explore the role and mechanism of T-cadherin(T-cad)in the occurrence and progression of bladder cancer.Methods The differential expression of T-cad mRNA in the serum of bladder cancer patients and Control group was detected.The clinical staging and tumor histopathological grading were compared between bladder cancer patients with low T-cad expression and high T-cad expression.An EJ1 cell line overexpressing T-cad was established,and the effects of T-cad overexpression on cell proliferation and colony formation ability were assessed using CCK-8 and clone formation assays,respectively.The impact of T-cad overexpression on the PI3K-AKT signaling pathway in EJ1 cells was analyzed using Western blotting.Results Compared to the control group,bladder cancer patients exhibited lower levels of T-cad mRNA expression in the serum(P<0.001).Bladder cancer patients with low T-cad expression showed higher pathological grades(P<0.05).T-cad overexpression inhibited cell proliferation(P<0.0001)and colony formation(P<0.05)ability in EJ1 cells.Furthermore,T-cad overexpression downregulated the expression levels of EGFR(P<0.01),PI3Kα(P<0.001),and p-AKT(P<0.001)in EJ1 cells.Conclusion T-cad suppresses the development of bladder cancer by downregulating the EGFR-PI3K-AKT signaling axis.