title: Citrate synthase expression affects tumor phenotype and drug resistance in human ovarian carcinoma.
abstract: Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Lilan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Di
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, P. R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D002950:Citrate (si)-Synthase / Q000235:genetics* / Q000378:metabolism*; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D002945:Cisplatin