Overexpression of DAXX enhanced
ovarian cancer cell proliferation, colony formation, and migration, whereas Daxx depletion had the opposite effects.
CONCLUSION: ModulatingDAXXmay be an effective strategy for preventing the recurrence and chemoresistance of
ovarian cancers. Understanding the genes involved in apoptosis and DNA damage responses may improve therapeutic strategies for
ovarian cancer. The death domain-associated
protein DAXX can be either a pro-apoptotic or an anti-apoptotic factor, depending on the cell type and context. In this study, we found that DAXX was highly expressed in human ovarian surface epithelial
tumors but not in
granulosa cell tumors. In cultured
ovarian cancer cells, DAXX interacted with
promyelocytic leukemia protein (PML) and localized to subnuclear domains (so-called PML nuclear bodies). A role for DAXX in
ovarian cancer cell proliferation,
metastasis, and radio/chemoresistance was examined. Overexpression of DAXX enhanced multiple
ovarian cancer cell lines' proliferation, colony formation, and migration, whereas Daxx depletion by RNA interference had the opposite effects. When transplanted into nude mice,
ovarian cancer cells that overexpressed DAXX displayed enhanced
tumorigenesis capability in vivo, whereas Daxx depletion inhibited
tumor development. Importantly, Daxx induced
tumorigenic transformation of normal ovarian surface epithelial cells. Daxx also protected
ovarian cancer cells against x-irradiation- and
chemotherapy-induced DNA damage by interacting with PML. Taken together, our results suggest that DAXX is a novel
ovarian cancer oncogene that promotes
ovarian cancer cell proliferation and chemoresistance in
ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an effective strategy for preventing the recurrence and chemoresistance of
ovarian cancers.