MAP4 phosphorylation induced by ARID1A loss sensitizes colorectal cancer cells to EMP.

ABSTRACT: Mutational inactivation of the tumor suppressor gene ARID1A is a key driver of tumorigenesis in various types of cancer, making it a promising therapeutic target for anticancer drug development. Here, we performed a synthetic lethal drug screening in an approved drug library with ARID1A isogenic CRC cell lines and identified estramustine phosphate sodium (EMP), an FDA approved antimicrotubule chemotherapy drug, as a synthetic lethal partner of ARID1A. ARID1A loss increases the vulnerability to EMP. Mechanistically, ARID1A loss increases the phosphorylation level of MAP4 (microtubule-associated protein 4), which is a key microtubule dynamics regulator in cancer cells. Therefore, ARID1A loss attenuates microtubule stabilizing activity of MAP4 and creates a dependence on its residual activity

SUBMITTER: Pan L 

PROVIDER: S-EPMC12830715 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature