{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:21Z","timestamp":1790920521166,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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.\n                      <jats:italic>In vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments were subsequently performed to characterize the biological functions of the ESCO1\/NUFIP2 axis and elucidate its underlying molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vivo<\/jats:italic>\n                      , 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1929713","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:35:19Z","timestamp":1790919319000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ESCO1 stabilizes NUFIP2 through acetylation\u2013ubiquitination crosstalk to promote pancreatic cancer progression"],"prefix":"10.3389","volume":"17","author":[{"given":"Letian","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, 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