Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Chloride channel-3 promotes tumor metastasis by regulating membrane ruffling and is associated with poor survival.

Authors: Bin Xu, Xiaobao Jin, Ling Min, Qin Li, Lulu Deng, Hui Wu, Guixian Lin, Lixin Chen, Haifeng Zhang, ChunMei Li, Liwei Wang, Jiayong Zhu, Weizhang Wang, Fujiang Chu, Juan Shen, Hongzhi Li, Jianwen Mao

Journal, date & volume: Oncotarget, 2015 Feb 10 , 6, 2434-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25537517

Abstract
The chloride channel-3 (ClC-3) protein is known to be a component of Cl- channels involved in cell volume regulation or acidification of intracellular vesicles. Here, we report that ClC-3 was highly expressed in the cytoplasm of metastatic carcinomatous cells and accelerated cell migration in vitro and tumor metastasis in vivo. High-grade expression of cytoplasmic ClC-3 predicted poor survival in cancer patients. We found that independent of its volume-activated Cl- channel properties, ClC-3 was able to promote cell membrane ruffling, required for tumor metastasis. ClC-3 mediated membrane ruffling by regulating keratin 18 phosphorylation to control β1 Integrin recycling. Therefore, cytoplasmic ClC-3 plays an active and key role in tumor metastasis and may be a valuable prognostic biomarker and a therapeutic target to prevent tumor spread.