DDB2 Suppresses Tumorigenicity by Limiting the Cancer Stem Cell Population in Ovarian Cancer
2014
Ovarian cancer is an extremely aggressive disease associated with a high percentage of tumor recurrence and chemotherapyresistance.Understandingtheunderlyingmechanismoftumorrelapseiscrucialforeffectivetherapy 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 capabilitytorecapitulatetumorsinathymicnudemice.MechanisticinvestigationdemonstratedthatDDB2isable toreducethecancerstemcell(CSC)populationcharacterizedwithhighaldehydedehydrogenaseactivityinovarian 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. Implications:DDB2statushasprognosticpotential,andelevatingitsexpressioneradicatesCSCsandcouldreduce ovarian cancer relapse. Mol Cancer Res; 1–11. � 2014 AACR.
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