Identification and validation of differentially expressed proteins in epithelial ovarian cancers using quantitative proteomics.
Ovarian cancer is the most lethal gynecological malignant tumor because of its high recurrence rate. In the present work, in order to find new therapeutic targets, we identified 8480 proteins in thirteen pairs of ovarian cancer tissues and normal ovary tissues through quantitative proteomics. 498 proteins were found to be differentially expressed in ovarian cancer, which involved in various cellular processes, including metabolism, response to stimulus and biosynthetic process. The expression levels of chloride intracellular channel protein 1 (CLIC1) and lectin galactoside-binding soluble 3 binding protein (LGALS3BP) in epithelial ovarian cancer tissues were significantly higher than those in normal ovary tissues as confirmed by western blotting and immunohistochemistry. The knockdown of CLIC1 in A2780 cell line downregulated expression of CTPS1, leading to the decrease of CTP and an arrest of cell cycle G1 phase, which results into a slower proliferation. CLIC1-knockdown can also slow down the tumor growth in vivo. Besides, CLIC1-knockdown cells showed an increased sensitivity to hydrogen peroxide and cisplatin, suggesting that CLIC1 was involved in regulation of redox and drug resistance in ovarian cancer cells. These results indicate CLIC1 promotes tumorgenesis, and is a potential therapeutic target in epithelial ovarian cancer treatment.
Department of Obstetrics & Gynecology, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing, China.
Hong
H
Qu
Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China.|MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Yuling
Y
Chen
Department of Obstetrics & Gynecology, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing, China.
Guangming
G
Cao
Department of Obstetrics & Gynecology, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing, China.
Chongdong
C
Liu
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Jiatong
J
Xu
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Haiteng
H
Deng
Department of Obstetrics & Gynecology, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing, China.
Zhenyu
Z
Zhang
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D003570:Cytidine Triphosphate / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D015203:Reproducibility of Results; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D016326:Extracellular Matrix Proteins
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019731:Carbon-Nitrogen Ligases; D002352:Carrier Proteins; D018118:Chloride Channels; D002945:Cisplatin; D003570:Cytidine Triphosphate; D006023:Glycoproteins; D006861:Hydrogen Peroxide; C501966:CLIC1 protein, human; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins; C019951:CTP synthetase
CLIC1; LGALS3BP; epithelial ovarian cancer; proteomics; therapeutic target