Abstract / Summary
Background Pancreatic cancer is a highly aggressive malignancy with a poor prognosis, and its molecular pathogenesis remains incompletely understood, with effective therapeutic options still limited. Establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) has been implicated in the development and progression of several malignancies; however, its biological role and underlying mechanisms in pancreatic cancer remain largely unknown. This study aimed to elucidate the clinical significance and molecular mechanisms of the ESCO1/NUFIP2 axis in pancreatic cancer. Methods TCGA, CPTAC, and other publicly available datasets were used to evaluate the expression patterns, diagnostic value, and prognostic significance of ESCO1 and NUFIP2 in pancreatic cancer. In vitro and in vivo experiments were subsequently performed to characterize the biological functions of the ESCO1/NUFIP2 axis and elucidate its underlying molecular mechanisms. Results ESCO1 and NUFIP2 were significantly upregulated in pancreatic cancer and were associated with poor prognosis. Functional assays demonstrated that the ESCO1/NUFIP2 axis promoted pancreatic cancer cell proliferation and migration, enhanced tumor growth in vivo , and suppressed apoptosis. Mechanistically, ESCO1 promoted NUFIP2 acetylation and limited its K48-linked ubiquitination and subsequent degradation, thereby maintaining NUFIP2 protein stability. Stabilized NUFIP2 preserved mitochondrial function and suppressed mitochondrial apoptosis, whereas NUFIP2 overexpression or trichostatin A (TSA) treatment partially reversed the effects of ESCO1 depletion. Moreover, the ESCO1/NUFIP2 axis was associated with immune cell infiltration, and depletion of either ESCO1 or NUFIP2 enhanced dendritic cell (DC)-mediated cytotoxic T lymphocyte (CTL) antitumor responses. Conclusion ESCO1 stabilizes NUFIP2 through acetylation-dependent regulation, thereby preserving mitochondrial function, suppressing mitochondrial apoptosis, and promoting pancreatic cancer progression. The ESCO1/NUFIP2 axis may also contribute to the regulation of antitumor immunity, highlighting its potential as a biomarker and therapeutic target in pancreatic cancer.