TrpC5 regulates differentiation through the Ca2+-Wnt5a signal pathway in colorectal cancer

Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca2+ channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca2+]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness. Notably, patients with tumors that expressed high levels of TrpC5 showed significantly poorer disease-free survival and overall survival. Therefore, our findings suggest that TrpC5 is an independent adverse prognostic factor for death in colorectal cancer reducing differentiation through the Ca2+-Wnt5a signal pathway.

Source: Clinical Science - November 27, 2016 Category: Biomedical Science Authors: Chen, Z., Tang, C., Zhu, Y., Xie, M., He, D., Pan, Q., Zhang, P., Hua, D., Wang, T., Jin, L., Qi, X., Zhu, Y., Yao, X., Jin, J., Ma, X. Tags: PublishAheadOfPrint Source Type: research