title: Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells.
abstract: 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.
authors.affiliation: School of Medicine and Pharmaceutics,  Jiangnan University, Wuxi, Jiangsu 214122,  China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Cai
authors.forename: Dongxu
authors.initials: D
authors.lastname: He
authors.forename: Chang
authors.initials: C
authors.lastname: Zou
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Chun Yin
authors.initials: CY
authors.lastname: Lo
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.forename: Franky L
authors.initials: FL
authors.lastname: Chan
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Zhu
authors.forename: Jianyong
authors.initials: J
authors.lastname: Lei
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004317:Doxorubicin; D018432:Drug Resistance, Multiple / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D050778:NFATC Transcription Factors / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015398:Signal Transduction / Q000502:physiology*; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D050778:NFATC Transcription Factors; D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse; C445503:transcription factor NF-AT c3; D004317:Doxorubicin; D008156:Luciferases