MARK2 regulates chemotherapeutic responses through class IIa HDAC-YAP axis in pancreatic cancer.

ABSTRACT: Despite paclitaxel's wide use in cancer treatment, patient response rate is still low and drug resistance is a major clinical obstacle. Through a Phos-tag-based kinome-wide screen, we identified MARK2 as a critical regulator for paclitaxel chemosensitivity in PDAC. We show that MARK2 is phosphorylated by CDK1 in response to antitubulin chemotherapeutics and in unperturbed mitosis. Phosphorylation is essential for MARK2 in regulating mitotic progression and paclitaxel cytotoxicity in PDAC cells. Mechanistically, our findings also suggest that MARK2 controls paclitaxel chemosensitivity by regulating class IIa HDACs. MARK2 directly phosphorylates HDAC4 specifically during antitubulin treatment. Phosphorylated HDAC4 promotes YAP activation and controls expression of YAP target genes induced by

SUBMITTER: Zeng Y 

PROVIDER: S-EPMC9339507 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature