{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:07:49Z","timestamp":1792786069228,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CPSF","award":["GZC20251903"],"award-info":[{"award-number":["GZC20251903"]}]},{"name":"Funding of Sichuan Provincial People\u2019s hospital","award":["25QNPY030"],"award-info":[{"award-number":["25QNPY030"]}],"id":[{"id":"https:\/\/ror.org\/03wwr4r78","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373131"],"award-info":[{"award-number":["82373131"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573142"],"award-info":[{"award-number":["82573142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472640"],"award-info":[{"award-number":["82472640"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Oriental Talent Program","award":["QNKJ2024022"],"award-info":[{"award-number":["QNKJ2024022"]}]},{"name":"Physician-Scientist Development"},{"name":"Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine","award":["AJ1-0204-00\u20130236"],"award-info":[{"award-number":["AJ1-0204-00\u20130236"]}],"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Silent corticotroph adenomas (SCAs) are an aggressive pituitary neuroendocrine tumor (PitNET) subtype lacking effective medical therapies and showing a high rate of recurrence. The molecular mechanisms driving their proliferation remain poorly understood. Although metabolic reprogramming is a hallmark of cancer, neither lipid metabolism nor its regulatory pathways have been systematically investigated in SCAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrative analyses of bulk and single-cell RNA sequencing datasets from SCAs, functioning corticotroph adenomas (FCAs), and normal pituitary tissue to characterize GAL expression and associated signaling pathways. Mechanistic studies employed GAL gain- and loss-of-function models, RNA sequencing, luciferase reporter assays, lipidomics, and pharmacological inhibition. Regulation of GAL by MYCN was assessed through promoter transactivation assays. The therapeutic efficacy of SREBP1 inhibition (fatostatin) was evaluated both in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a marked downregulation of galanin (GAL) in SCAs and demonstrated that GAL loss promotes tumor cell proliferation. GAL deficiency activated the PI3K\u2013Akt\u2013mTOR signaling cascade, resulting in increased activity of SREBP1, a key transcriptional regulator of lipogenesis. Enhanced fatty-acid synthesis provided metabolic support for SCA growth. We further uncovered a linear regulatory axis in which MYCN directly upregulates GAL; however, MYCN downregulation in SCAs suppresses GAL expression, thereby enabling SREBP1-driven lipogenesis. Pharmacological inhibition of SREBP1 with fatostatin reduced lipogenesis and significantly suppressed SCA growth in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal a previously unrecognized MYCN\u2013GAL\u2013SREBP1 lipogenic axis that drives SCA proliferation. SREBP1-dependent lipogenesis represents a promising and druggable therapeutic vulnerability for the treatment of SCAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag141","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:44:02Z","timestamp":1782233042000},"page":"2401-2416","source":"Crossref","is-referenced-by-count":0,"title":["A MYCN\u2013GAL\u2013SREBP1 lipogenic axis drives proliferation in silent corticotroph adenomas"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-7711","authenticated-orcid":false,"given":"Changxi","family":"Han","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8477-8221","authenticated-orcid":false,"given":"Junchen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3278-2812","authenticated-orcid":false,"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongze","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6595-3744","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5531-2063","authenticated-orcid":false,"given":"Yihan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0495-8711","authenticated-orcid":false,"given":"Qiuyue","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3160-2828","authenticated-orcid":false,"given":"Zhuoyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China , 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