Overexpression of TrpC5 promotes tumor metastasis via the HIF-1{alpha}/Twist signaling pathway in colon cancer

In cancer cells, the intracellular Ca2+ ([Ca2+]i) 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 TrpC5 caused a robust [Ca2+]i rise, 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 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.

Source: Clinical Science - September 1, 2017 Category: Biomedical Science Authors: Chen, Z., Zhu, Y., Dong, Y., Zhang, P., Han, X., Jin, J., Ma, X. Tags: PublishAheadOfPrint Source Type: research