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

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.

SUBMITTER: Xu B 

PROVIDER: S-EPMC4385862 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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

Xu Bin B   Jin Xiaobao X   Min Ling L   Li Qin Q   Deng Lulu L   Wu Hui H   Lin Guixian G   Chen Lixin L   Zhang Haifeng H   Li Chunmei C   Wang Liwei L   Zhu Jiayong J   Wang Weizhang W   Chu Fujiang F   Shen Juan J   Li Hongzhi H   Mao Jianwen J  

Oncotarget 20150201 4

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  ...[more]

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