Disruption of ARID1B Recruitment to the Nuclear Pore Complex as a New Anticancer Therapeutic Strategy.

ABSTRACT: Triple-negative breast cancer (TNBC), a highly aggressive subtype, currently lacks potent targeted therapies. ARID1B, a key SWI/SNF chromatin remodeling complex subunit, is linked to high-grade malignancies and poor prognosis, making it a potential biomarker and therapeutic target. However, its function and regulation remain unclear. Here, it is found that uncontrolled accumulation of ARID1B and its dysregulated nuclear import promoted oncogenesis and drug resistance. ARID1B negatively regulates ARID1A, impairing SWI/SNF-mediated tumor suppression and enhancing tumor survival. Using protein complex purification and mass spectrometry, the KPNA2-KPNB1-RANBP2 protein cascade is identified as critical for facilitating ARID1B nuclear import. Replacing R1518, H1519, and D1522 residues on ARID1B

SUBMITTER: Odnokoz O 

PROVIDER: S-EPMC12463049 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature