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However, the underlying mechanism remains unclear. Here, by enrolling independent ESCC cohorts, we verified the negative correlation between intratumoral FBL expression and patient prognosis. Notably, comprehensive transcriptomic and metabolomic analyses indicated that\n                    <jats:italic>FBL<\/jats:italic>\n                    deletion elicited cell cycle arrest and cellular senescence, as well as block of nicotinamide metabolism and increase of oxidative stress. Mechanistically, FBL could bind to and stabilize SIRT1 by obstructing the ubiquitin\u2010proteasome\u2010mediated protein degradation, therefore provoking nicotinamide metabolism, sustaining redox homeostasis, and counteracting senescence. Clinically, FBL\u2010SIRT1 axis was augmented in tumor tissues of ESCC patients, and high intratumoral SIRT1 expression predicted poor patient survival. Finally, we found that both genetic and pharmacological inhibition of FBL could sensitize senolytic therapy for ESCC. In conclusion, we first discovered FBL as an anti\u2010senescent protein in tumor progression. FBL resists cellular senescence by stabilizing SIRT1 and sustaining the nicotinamide metabolism, therefore providing an optional strategy for ESCC treatment by sensitizing senolytic therapy with FBL inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/advs.76962","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:41:02Z","timestamp":1786358462000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibrillarin Resists Cellular Senescence Via SIRT1\u2010Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-1469","authenticated-orcid":false,"given":"Xing","family":"Jin","sequence":"first","affiliation":[{"name":"Cancer Institute Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5756-0455","authenticated-orcid":false,"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Institute Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Gao","sequence":"additional","affiliation":[{"name":"Cancer Institute Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation  Shanghai 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of Thoracic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-9940","authenticated-orcid":false,"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Cancer Institute Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Department of Medical Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Feng","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy for Medical Sciences and Peking Union Medical College  Beijing 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