{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:06:32Z","timestamp":1772712392528,"version":"3.50.1"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,8]]},"abstract":"<jats:p>\n            Gallbladder cancer (GBC) is the most common malignancy in the biliary system and lacks biomarkers for personalized therapy. Here, we reported that hepatic leukemia factor (HLF) was highly expressed in gallbladder cancer stem cells (CSCs) and patients with gemcitabine-resistant GBC. Mechanistic study revealed that interleukin-6 receptor (IL-6R) and transcription factor EB (TFEB) are direct target genes of HLF. The IL-6\/IL-6R\/signal transducer and activator of transcription 3 axis transactivates HLF expression in GBC, forming a positive feedback loop. Functional studies revealed that HLF promoted gallbladder CSCs\u2019 expansion and gemcitabine resistance via TFEB-induced autophagy. In addition, HLF drives TFEB-induced programmed death ligand 1 expression in human tumors and governs tumor immune evasion in a CD8\n            <jats:sup>+<\/jats:sup>\n            T cell\u2013dependent manner. Patient cohorts\u2019 analysis suggested that HLF levels in GBCs might determine the distinct responses to chemotherapy and immunotherapy. In conclusion, our findings demonstrated that HLF could act as a driver for gallbladder CSCs\u2019 self-renewal and drug resistance and a biomarker for individualized therapy.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adv6723","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T17:58:46Z","timestamp":1754675926000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["HLF transactivates\n            <i>TFEB<\/i>\n            to promote gallbladder cancer stem cells\u2019 self-renewal and determines tumor response to distinct therapies"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-8082","authenticated-orcid":true,"given":"Daimin","family":"Xiang","sequence":"first","affiliation":[{"name":"International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China."},{"name":"Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-6127","authenticated-orcid":true,"given":"Zhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Third Affiliated Hospital of Naval Military Medical University, Shanghai 200438, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1082-2881","authenticated-orcid":true,"given":"Mingye","family":"Gu","sequence":"additional","affiliation":[{"name":"International Cooperation Laboratory on Signal Transduction, National Center for Liver Cancer, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China."},{"name":"State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong 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