TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in colorectal cancer
TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in colorectal cancer
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TrpC5 通过 Ca2 /Wnt5a 信号通路调节结直肠癌分化
DOI：
10.1042/cs20160759
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发表时间：
2017-02-01
期刊：
影响因子：
6
通讯作者：
Ma, Xin
中科院分区：
文献类型：
--
作者：
Chen, Zhen;Tang, Chunlei;Ma, Xin
瞬时受体电位通道5（TrpC 5）是TrpC亚组的成员，并且其形成受体激活的非选择性Ca 2+通道。TrpC 5通道的结构知之甚少。在本研究中，我们报告说，TrpC 5是一个关键因素，在调节分化的结直肠癌（CRC）。通过对来自一个大的CRC患者队列的标本的研究，我们发现TrpC 5是高表达的，其细胞水平与肿瘤分级相关。我们进一步表明，上调的TrpC 5引起细胞内钙浓度[Ca 2 +] i的强劲上升，增加Wnt 5a表达和β-连环蛋白的核转位，导致癌症分化的减少和癌细胞干细胞性的增加。值得注意的是，表达高水平TrpC 5的肿瘤患者的无病生存率和总生存率明显较差。因此，我们的研究结果表明，TrpC 5是一个独立的不利预后因素，死亡的CRC，减少分化通过Ca 2 +/Wnt 5a信号通路。
Transient receptor potential channel 5 (TrpC5) is a member of the TrpC subgroup, and it forms a receptor-activated, non-selective Ca2+ channel. The architecture of the TrpC5 channel is poorly understood. In the present study, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer (CRC). Through a study of specimens from a large cohort of patients with CRC, we found that TrpC5 was highly expressed and its cellular level correlated with tumour grade. We showed further that up-regulated TrpC5 caused a robust rise in intracellular calcium concentration [Ca2+] i, increased Wnt5a expression and the nuclear translocation of beta-catenin, leading to a reduction in cancer differentiation and an increase in cancer cell stemness. Notably, patients with tumours that expressed high levels of TrpC5 showed significantly poorer disease-free and overall survival. Therefore, our findings suggest that TrpC5 is an independent adverse prognostic factor for death in CRC, reducing differentiation through the Ca2+/Wnt5a signalling pathway.