PRMT1-catalyzed NUSAP1 methylation enhances Notch2 signaling and 5-FU resistance in gastric cancer.

ABSTRACT: 5-Fluorouracil (5-FU) resistance remains a significant challenge in the treatment of gastric cancer, limiting its clinical efficacy. Our study identifies NUSAP1, a nucleolar and spindle-associated protein, as a key driver of 5-FU resistance in gastric cancer. Proteomic analyses of 5-FU-resistant gastric cancer cell lines revealed that NUSAP1 is significantly upregulated, and functional studies demonstrated its essential role in promoting resistance, proliferation, migration, invasion, and tumor growth. Mechanistic investigations revealed that NUSAP1 undergoes asymmetric dimethylation (ADMA) at R418 and R422, mediated by PRMT1, with the R422 site being critical for its function. NUSAP1 interacts with the PEST domain of Notch2 through its R422 site, inhibiting Notch2 ubiquitination and stabi

SUBMITTER: Jiang S 

PROVIDER: S-EPMC12092681 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature