Inhibition of BAD-Ser99 phosphorylation synergizes with PARP inhibition to ablate PTEN-deficient endometrial carcinoma.

ABSTRACT: Loss of phosphatase and tensin homolog (PTEN) impairs DNA double-strand repair and confers sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPis). However, PARPis also hyperactivate the MAPK and PI3K/AKT/mTOR pathways in PTEN-deficient endometrial carcinoma (EC), which allows the emergence of PARPi resistance. BCL-2-associated death promoter (BAD), integrates the common cell survival effects of the RAS/MEK/MAPK and PI3K/AKT/mTOR pathways. Herein, it was observed that increased BADSer99 (BADS99) phosphorylation in EC cells was significantly associated with PTEN-deficient status. Forced expression of phosphorylation deficient human BADS99A in PTEN-deficient EC cells significantly increased CASPASE 3/7 activity and decreased EC cell viability. Using NPB as a pharmacological inhibitor

SUBMITTER: Zhang X 

PROVIDER: S-EPMC9209517 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature