Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway.

ABSTRACT: Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin-dependent kinases (CDKs), and the G1/S-phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8382979 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature