Close
Close

Ovarian cancer

Aurora A kinase regulates non-homologous end-joining and poly(ADP-ribose) polymerase function in ovarian carcinoma cells.
Related Articles

Aurora A kinase regulates non-homologous end-joining and poly(ADP-ribose) polymerase function in ovarian carcinoma cells.

Oncotarget. 2017 Jul 05;:

Authors: Do TV, Hirst J, Hyter S, Roby KF, Godwin AK

Abstract
Ovarian cancer is usually diagnosed at late stages when cancer has spread beyond the ovary and patients ultimately succumb to the development of drug-resistant disease. There is an urgent and unmet need to develop therapeutic strategies that effectively treat ovarian cancer and this requires a better understanding of signaling pathways important for ovarian cancer progression. Aurora A kinase (AURKA) plays an important role in ovarian cancer progression by mediating mitosis and chromosomal instability. In the current study, we investigated the role of AURKA in regulating the DNA damage response and DNA repair in ovarian carcinoma cells. We discovered that AURKA modulated the expression and activity of PARP, a crucial mediator of DNA repair that is a target of therapeutic interest for the treatment of ovarian and other cancers. Further, specific inhibition of AURKA activity with the small molecule inhibitor, alisertib, stimulated the non-homologous end-joining (NHEJ) repair pathway by elevating DNA-PKcs activity, a catalytic subunit required for double-strand break (DSB) repair, as well as decreased the expression of PARP and BRCA1/2, which are required for high-fidelity homologous recombination-based DNA repair. Further, AURKA inhibition stimulates error-prone NHEJ repair of DNA double-strand breaks with incompatible ends. Consistent with in vitro findings, alisertib treatment increased phosphorylated DNA-PKcs(pDNA-PKcsT2609) and decreased PARP levels in vivo. Collectively, these results reveal new non-mitotic functions for AURKA in the regulation of DNA repair, which may inform of new therapeutic targets and strategies for treating ovarian cancer.

PMID: 28700980 [PubMed - as supplied by publisher]

Videos
by Abidemi Uruejoma
45 views
by Abidemi Uruejoma
63 views
by Abidemi Uruejoma
68 views
Latest Research