In cancer cells, intracellular Ca2+ homeostasis is altered, and this is involved in tumor initiation, progression, and metastasis. However, little is known about the underlying mechanisms. Here, we report that transient receptor potential channel 5 (TrpC5), a receptor-activated non-selective Ca2+ channel, is correlated with tumor metastasis in colon cancer patients. Moreover, in colon cancer cells, overexpression of TrpC5 caused a robust rise in the concentration of ([Ca2+]i), decreased E-cadherin, and increased mesenchymal biomarker expression, then promoted cell migration, invasion, and proliferation. Interestingly, we found that TrpC5 mediated hypoxia-inducible factor 1α (HIF-1α) expression, activating Twist to promote the epithelial–mesenchymal transition (EMT). Notably, patients with high expression of TrpC5 displayed poorer overall and metastasis-free survival. Taken together, our findings demonstrate that TrpC5 induces the EMT through the HIF-1α–Twist signaling pathway to promote tumor metastasis in colon cancer.
Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α–Twist signaling pathway in colon cancer
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Zhen Chen, Yaodan Zhu, Yongfei Dong, Peng Zhang, Xiping Han, Jian Jin, Xin Ma; Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α–Twist signaling pathway in colon cancer. Clin Sci (Lond) 1 October 2017; 131 (19): 2439–2450. doi: https://doi.org/10.1042/CS20171069
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