title: Oncogenic roles of carbonic anhydrase 8 in human osteosarcoma cells.
abstract: Carbonic anhydrase 8 (CA8), a member of the carbonic anhydrase family, is one of the three isozymes that do not catalyze the reversible hydration of carbon dioxide due to the lack of one important histidine. In the present study, we observed increased expression of CA8 in more aggressive types of human osteosarcoma (OS) cells and found that CA8 expression is correlated with disease stages, such that more intense expression occurs in the disease late stage. We also demonstrated that overexpression of CA8 in human OS (HOS) cells significantly increased cell proliferation both in vitro and in vivo. Downregulated CA8 sensitized cells to apoptotic stress induced by staurosporine and cisplatin, suggesting a specific role of CA8 to protect cells from stresses. In addition, downregulation of CA8 in HOS cells reduced cell invasion and colony formation ability in soft agar and further decreased matrix metalloproteinase 9 and focal adhesion kinase expression, indicating that CA8 might facilitate cancer cell invasion via the activation of FAK-MMP9 signaling. Interestingly, HOS cells with CA8 knockdown showed a significant decrease in glycolytic activity and cell death under glucose withdrawal, further indicating that CA8 may be involved in regulating aerobic glycolysis and enhancing cell viability. Knockdown of CA8 significantly decreased phosphorylated Akt expression suggesting that the oncogenic role of CA8 may be mediated by the regulation of Akt activation through p-Akt induction. Importantly, the inhibition of glycolysis by 2-deoxyglucose sensitized CA8 HOS-CA8-myc cells to cisplatin treatment under low glucose condition, highlighting a new therapeutic option for OS cancer.
authors.affiliation: Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Republic of China.
authors.forename: Tze-Kai
authors.initials: TK
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Republic of China.
authors.forename: Che-Min
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
authors.affiliation: Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Chieh-Lin Jerry
authors.initials: CL
authors.lastname: Teng
authors.affiliation: Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Republic of China.|Life Science Research Center, Tunghai University, Taichung, Taiwan, Republic of China.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Chao
authors.affiliation: Life Science Research Center, Tunghai University, Taichung, Taiwan, Republic of China.|Physical Education Office, Tunghai University, Taichung, Taiwan, Republic of China.
authors.forename: Min Huan
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan, Republic of China.
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung, 407, Taiwan, Republic of China. mhsieh@thu.edu.tw.|Life Science Research Center, Tunghai University, Taichung, Taiwan, Republic of China. mhsieh@thu.edu.tw.
authors.forename: Mingli
authors.initials: M
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009857:Oncogenes; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin; C512818:CA8 protein, human; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
keywords: 2-Deoxy-D-glucose; Carbonic anhydrase 8; Cell migration; Cisplatin; Osteosarcoma; Proliferation