Lin Jianqing, Chen Zhiyao, Huang Zhijun, Chen Feng, Ye Zeyi, Lin Shaoze, Wang Weidong
Department of Surgical Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4194-4200. doi: 10.3892/etm.2017.5090. Epub 2017 Sep 1.
As a unique member of the cadherin superfamily, T-cadherin (T-cad) has been demonstrated to be associated with gastric cancer (GC) prognosis. To elucidate the function of T-cad in GC , the present study firstly examined T-cad protein expression in normal and gastric cancer tissues and cell lines, and it was demonstrated to be significantly downregulated in gastric cancer samples compared with normal samples. Control and T-cad expression vectors were then transfected into the MGC8-03 and AGS GC cell lines. Utilizing MTT, clonogenic, flow cytometry, wound healing and Transwell invasion assays in addition to Western blotting, the present study demonstrated that the overexpression of T-cad suppressed GC cell growth and colony formation via cell cycle arrest at the G0/G1 phase via downregulating the expression of cyclin dependent kinase 4 and Cyclin D1. In addition, overexpression of T-cad significantly inhibited GC cell migration and invasion by increasing E-cadherin and decreasing Vimentin expression. These findings suggest T-cad may be important in GC cell proliferation and metastasis and serve as a promising target for the treatment of GC in the future.
作为钙黏蛋白超家族的独特成员，T-钙黏蛋白（T-cad）已被证明与胃癌（GC）的预后相关。为阐明T-cad在胃癌中的功能，本研究首先检测了正常组织、胃癌组织及细胞系中T-cad蛋白的表达，结果显示与正常样本相比，胃癌样本中T-cad蛋白表达显著下调。随后将对照载体和T-cad表达载体转染至MGC8-03和AGS胃癌细胞系。本研究通过MTT法、克隆形成实验、流式细胞术、伤口愈合实验、Transwell侵袭实验以及蛋白质免疫印迹法，证明T-cad的过表达通过下调细胞周期蛋白依赖性激酶4和细胞周期蛋白D1的表达，使细胞周期阻滞于G0/G1期，从而抑制胃癌细胞的生长和集落形成。此外，T-cad的过表达通过增加E-钙黏蛋白表达、降低波形蛋白表达，显著抑制胃癌细胞的迁移和侵袭。这些研究结果表明，T-cad可能在胃癌细胞增殖和转移过程中发挥重要作用，有望成为未来胃癌治疗的靶点。
