PubMed 22988121

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC5

Title: Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells.

Authors: Xin Ma, Yanfei Cai, Dongxu He, Chang Zou, Peng Zhang, Chun Yin Lo, Zhenyu Xu, Franky L Chan, Shan Yu, Yun Chen, Ruiyu Zhu, Jianyong Lei, Jian Jin, Xiaoqiang Yao

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2012 Oct 2 , 109, 16282-7

PubMed link:

An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca(2+)-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell line MCF-7/ADM. Suppressing TRPC5 activity/expression reduced the P-gp induction and caused a remarkable reversal of adriamycin resistance in MCF-7/ADM. In an athymic nude mouse model of adriamycin-resistant human breast tumor, suppressing TRPC5 decreased the growth of tumor xenografts. Nuclear factor of activated T cells isoform c3 (NFATc3) was the transcriptional factor that links the TRPC5 activity to P-gp production. Together, we demonstrated an essential role of TRPC5-NFATc3-P-gp signaling cascade in P-gp induction in drug-resistant cancer cells.