期刊
ONCOTARGET
卷 6, 期 4, 页码 2434-2450出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2966
关键词
chloride channel-3; tumor metastasis; membrane ruffling; cell migration
资金
- National Natural Science Foundation of China [31371144, 30800435, 81170339, 81101666, 81272223, 81273539]
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 beta 1 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.
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