title: DDB2 suppresses tumorigenicity by limiting the cancer stem cell population in ovarian cancer.
abstract: Ovarian cancer is an extremely aggressive disease associated with a high percentage of tumor recurrence and chemotherapy resistance. Understanding the underlying mechanism of tumor relapse is crucial for effective therapy of ovarian cancer. DNA damage-binding protein 2 (DDB2) is a DNA repair factor mainly involved in nucleotide excision repair. Here, a novel role was identified for DDB2 in the tumorigenesis of ovarian cancer cells and the prognosis of patients with ovarian cancer. Overexpressing DDB2 in human ovarian cancer cells suppressed its capability to recapitulate tumors in athymic nude mice. Mechanistic investigation demonstrated that DDB2 is able to reduce the cancer stem cell (CSC) population characterized with high aldehyde dehydrogenase activity in ovarian cancer cells, probably through disrupting the self-renewal capacity of CSCs. Low DDB2 expression correlates with poor outcomes among patients with ovarian cancer, as revealed from the analysis of publicly available gene expression array datasets. Given the finding that DDB2 protein expression is low in ovarian tumor cells, enhancement of DDB2 expression is a promising strategy to eradicate CSCs and would help to halt ovarian cancer relapse.
  
  
  CONCLUSIONS
  DDB2 status has prognostic potential, and elevating its expression eradicates CSCs and could reduce ovarian cancer relapse.
authors.affiliation: Authors' Affiliations: Departments of Radiology and 2Pathology; 3Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; and 4Weifang Medical University, Shandong, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Han
authors.forename: Ran
authors.initials: R
authors.lastname: Zhao
authors.forename: Xingluo
authors.initials: X
authors.lastname: Liu
authors.forename: Amit
authors.initials: A
authors.lastname: Srivastava
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Hsiaoyin
authors.initials: H
authors.lastname: Mao
authors.forename: Meihua
authors.initials: M
authors.lastname: Qu
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Wang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins