Cell-specific mechanisms of TMEM16A Ca2+-activated chloride channel in cancer

Molecular Cancer

Review

Liang Zou¹  Qinghuan Xiao²  Hui Wang²  Ke Ma²  Jiankun Yu²  Minjie Wei³  Huizhe Wu³ 

[1] Department of Anesthesiology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China;Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, 110122, Shenyang, China;Department of Pharmacology, School of Pharmacy, China Medical University, 110122, Shenyang, China;

关键词: TMEM16A;    Anoctamin 1;    Ca-activated chloride channel;    Tumorigenesis;    Signaling;    Biomarker;   

DOI  :  10.1186/s12943-017-0720-x

 received in 2017-04-24, accepted in 2017-09-01,  发布年份 2017

来源: Springer

【 摘 要 】

TMEM16A (known as anoctamin 1) Ca2+-activated chloride channel is overexpressed in many tumors. TMEM16A overexpression can be caused by gene amplification in many tumors harboring 11q13 amplification. TMEM16A expression is also controlled in many cancer cells via transcriptional regulation, epigenetic regulation and microRNAs. In addition, TMEM16A activates different signaling pathways in different cancers, e.g. the EGFR and CAMKII signaling in breast cancer, the p38 and ERK1/2 signaling in hepatoma, the Ras-Raf-MEK-ERK1/2 signaling in head and neck squamous cell carcinoma and bladder cancer, and the NFκB signaling in glioma. Furthermore, TMEM16A overexpression has been reported to promote, inhibit, or produce no effects on cell proliferation and migration in different cancer cells. Since TMEM16A exerts different roles in different cancer cells via activation of distinct signaling pathways, we try to develop the idea that TMEM16A regulates cancer cell proliferation and migration in a cell-dependent mechanism. The cell-specific role of TMEM16A may depend on the cellular environment that is predetermined by TMEM16A overexpression mechanisms specific for a particular cancer type. TMEM16A may exert its cell-specific role via its associated protein networks, phosphorylation by different kinases, and involvement of different signaling pathways. In addition, we discuss the role of TMEM16A channel activity in cancer, and its clinical use as a prognostic and predictive marker in different cancers. This review highlights the cell-type specific mechanisms of TMEM16A in cancer, and envisions the promising use of TMEM16A inhibitors as a potential treatment for TMEM16A-overexpressing cancers.

【 授权许可】

CC BY   
© The Author(s). 2017