title: ClC-3 chloride channel modulates the proliferation and migration of osteosarcoma cells via AKT/GSK3β signaling pathway.
abstract: In cultured human osteosarcoma (OS) cells, we recently demonstrated that insulin-like growth factors (IGF-1)-induced MG-63 and 143B human OS cells proliferation were consistent with increasing ClC-3 expression, and ClC-3 was up-regulated in cells with high metastatic potency. Blockade of ClC-3 greatly suppressed the phosphorylation activation of Akt/GSK3β. We also found that blockade of ClC-3 effectively down-regulated the expression of cyclin D1 and cyclin E, and caused activation of p27(KIP) and p21(CIP). The synthesized effects on these proteins which play a major role in cell cycle regulation bring about G0/G1 cell cycle arrest in MG-63 cells, and finally abrogate the cell proliferation. Besides, ClC-3 deletion attenuates OS cell migration via down-regulation the expression of MMP-2 and MMP-9. Such information suggests that ClC-3 might be a potential target for anti-OS.
authors.affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University Shenyang, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Orthopedics, Shengjing Hospital of China Medical University Shenyang, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism*; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D034741:RNA, Small Interfering; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: AKT/GSK3β signaling pathway; ClC-3 chloride channel; osteosarcoma; proliferation and migration