{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:13:40Z","timestamp":1793826820572,"version":"4.6.1"},"reference-count":111,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"am","delay-in-days":331,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007259","name":"Stony Brook University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R01DK123079-01"],"award-info":[{"award-number":["1R01DK123079-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA240818"],"award-info":[{"award-number":["1R01CA240818"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFA0506000"],"award-info":[{"award-number":["2017YFA0506000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.canlet.2020.11.026","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T09:38:23Z","timestamp":1606642703000},"page":"5-13","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":93,"special_numbering":"C","title":["FGF21 in obesity and cancer: New insights"],"prefix":"10.1016","volume":"499","author":[{"given":"Weiqin","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-4820","authenticated-orcid":false,"given":"Yongde","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2020.11.026_bib1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0167-4781(00)00067-1","article-title":"Identification of a novel FGF, FGF-21, preferentially expressed in the liver","volume":"1492","author":"Nishimura","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.canlet.2020.11.026_bib2","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"Kharitonenkov","year":"2005","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.canlet.2020.11.026_bib3","doi-asserted-by":"crossref","first-page":"15694","DOI":"10.1074\/jbc.M601252200","article-title":"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family","volume":"281","author":"Zhang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2020.11.026_bib4","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/mc.20241","article-title":"Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis","volume":"45","author":"Huang","year":"2006","journal-title":"Mol. Carcinog."},{"key":"10.1016\/j.canlet.2020.11.026_bib5","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.cmet.2007.05.002","article-title":"Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states","volume":"5","author":"Badman","year":"2007","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cmet.2007.05.003","article-title":"Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21","volume":"5","author":"Inagaki","year":"2007","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib7","doi-asserted-by":"crossref","first-page":"26687","DOI":"10.1074\/jbc.M704165200","article-title":"Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21","volume":"282","author":"Kurosu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2020.11.026_bib8","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1073\/pnas.0701600104","article-title":"BetaKlotho is required for metabolic activity of fibroblast growth factor 21","volume":"104","author":"Ogawa","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2020.11.026_bib9","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1210\/me.2010-0142","article-title":"Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse","volume":"24","author":"Fon Tacer","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.canlet.2020.11.026_bib10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.molmet.2012.08.007","article-title":"The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue","volume":"2","author":"Adams","year":"2012","journal-title":"Mol Metab"},{"key":"10.1016\/j.canlet.2020.11.026_bib11","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004690","article-title":"Treating diabetes and obesity with an FGF21-mimetic antibody activating the betaKlotho\/FGFR1c receptor complex","volume":"4","author":"Foltz","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1743-7075-9-94","article-title":"Control of lipid metabolism by adipocyte FGFR1-mediated adipohepatic communication during hepatic stress","volume":"9","author":"Yang","year":"2012","journal-title":"Nutr. Metab."},{"key":"10.1016\/j.canlet.2020.11.026_bib13","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/nm.3249","article-title":"FGF21 regulates metabolism and circadian behavior by acting on the nervous system","volume":"19","author":"Bookout","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib14","doi-asserted-by":"crossref","unstructured":"B.M. Owen, A.L. Bookout, X. Ding, V.Y. Lin, S.D. Atkin, L. Gautron, S.A. Kliewer, D.J. Mangelsdorf, FGF21 contributes to neuroendocrine control of female reproduction, Nat. Med., 19 1153-1156.","DOI":"10.1038\/nm.3250"},{"key":"10.1016\/j.canlet.2020.11.026_bib15","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.1210\/en.2008-0816","article-title":"Fibroblast growth factor 21 corrects obesity in mice","volume":"149","author":"Coskun","year":"2008","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib16","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1210\/en.2006-1168","article-title":"The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21","volume":"148","author":"Kharitonenkov","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib17","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cmet.2014.07.012","article-title":"FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss","volume":"20","author":"Owen","year":"2014","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib18","unstructured":"A.L. Wu, G. Kolumam, S. Stawicki, Y. Chen, J. Li, J. Zavala-Solorio, K. Phamluong, B. Feng, L. Li, S. Marsters, L. Kates, N. van Bruggen, M. Leabman, A. Wong, D. West, H. Stern, E. Luis, H.S. Kim, D. Yansura, A.S. Peterson, E. Filvaroff, Y. Wu, J. Sonoda, Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1, Sci. Transl. Med., 3 113ra126."},{"key":"10.1016\/j.canlet.2020.11.026_bib19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2337\/db08-0392","article-title":"Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice","volume":"58","author":"Xu","year":"2009","journal-title":"Diabetes"},{"key":"10.1016\/j.canlet.2020.11.026_bib20","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ebiom.2015.05.028","article-title":"Sustained Brown fat stimulation and insulin sensitization by a humanized bispecific antibody agonist for fibroblast growth factor receptor 1\/betaKlotho complex","volume":"2","author":"Kolumam","year":"2015","journal-title":"EBioMedicine"},{"key":"10.1016\/j.canlet.2020.11.026_bib21","article-title":"FGF21 can Be mimicked in vitro and in vivo by a novel anti-FGFR1c\/beta-klotho bispecific protein","volume":"8","author":"Smith","year":"2013","journal-title":"PloS One"},{"key":"10.1016\/j.canlet.2020.11.026_bib22","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1210\/en.2016-1917","article-title":"A novel Fc FGF21 with improved resistance to proteolysis, increased affinity towards Beta-Klotho and enhanced efficacy in Mice and Cynomolgus Monkeys","volume":"158","author":"Stanislaus","year":"2017","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib23","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1124\/jpet.113.204420","article-title":"Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody","volume":"346","author":"Huang","year":"2013","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.canlet.2020.11.026_bib24","doi-asserted-by":"crossref","unstructured":"G. Gaich, J.Y. Chien, H. Fu, L.C. Glass, M.A. Deeg, W.L. Holland, A. Kharitonenkov, T. Bumol, H.K. Schilske, D.E. Moller, The effects of LY2405319, an FGF21 analog, in Obese Human Subjects with Type 2 Diabetes, Cell Metab, vol. 18 333-340.","DOI":"10.1016\/j.cmet.2013.08.005"},{"key":"10.1016\/j.canlet.2020.11.026_bib25","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cmet.2016.02.001","article-title":"A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects","volume":"23","author":"Talukdar","year":"2016","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature25451","article-title":"alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling","volume":"553","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2020.11.026_bib27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nature25010","article-title":"Structures of beta-klotho reveal a 'zip code'-like mechanism for endocrine FGF signalling","volume":"553","author":"Lee","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2020.11.026_bib28","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tips.2018.12.002","article-title":"Emerging structure-function paradigm of endocrine FGFs in metabolic diseases","volume":"40","author":"Luo","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.canlet.2020.11.026_bib29","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2016.12.004","article-title":"FGF21 is an exocrine pancreas secretagogue","volume":"25","author":"Coate","year":"2017","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib30","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.molmet.2017.08.004","article-title":"Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury","volume":"6","author":"Desai","year":"2017","journal-title":"Mol Metab"},{"key":"10.1016\/j.canlet.2020.11.026_bib31","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aay5186","article-title":"Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy","volume":"12","author":"Hernandez","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib32","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2019.07.030","article-title":"Oncogenic KRAS reduces expression of FGF21 in acinar cells to promote pancreatic tumorigenesis in mice on a high-fat diet","author":"Luo","year":"2019","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib33","doi-asserted-by":"crossref","first-page":"31026","DOI":"10.1038\/srep31026","article-title":"Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2020.11.026_bib34","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1016\/S0140-6736(18)31785-9","article-title":"Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial","volume":"392","author":"Sanyal","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.canlet.2020.11.026_bib35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.molmet.2018.03.002","article-title":"Deficiency of fibroblast growth factor 21 (FGF21) promotes hepatocellular carcinoma (HCC) in mice on a long term obesogenic diet","volume":"13","author":"Singhal","year":"2018","journal-title":"Mol Metab"},{"key":"10.1016\/j.canlet.2020.11.026_bib36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-nutr-071816-064800","article-title":"Fibroblast growth factor 21: a versatile regulator of metabolic homeostasis","volume":"38","author":"BonDurant","year":"2018","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.canlet.2020.11.026_bib37","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-physiol-021115-105339","article-title":"Understanding the physiology of FGF21","volume":"78","author":"Fisher","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.canlet.2020.11.026_bib38","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.tem.2015.09.007","article-title":"FGF21 revolutions: recent advances illuminating FGF21 biology and medicinal properties","volume":"26","author":"Kharitonenkov","year":"2015","journal-title":"Trends Endocrinol. Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib39","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cmet.2019.01.004","article-title":"A dozen years of discovery: insights into the physiology and pharmacology of FGF21","volume":"29","author":"Kliewer","year":"2019","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s11684-019-0711-y","article-title":"The FGF metabolic axis","volume":"13","author":"Li","year":"2019","journal-title":"Front. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib41","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.2337\/db05-1435","article-title":"Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1\/2 and Akt signaling pathways","volume":"55","author":"Wente","year":"2006","journal-title":"Diabetes"},{"key":"10.1016\/j.canlet.2020.11.026_bib42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0148252","article-title":"Fibroblast growth factor 21 (FGF21) protects against high fat diet induced inflammation and islet hyperplasia in pancreas","volume":"11","author":"Singhal","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.canlet.2020.11.026_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2015.80","article-title":"Loss of fibroblast growth factor 21 action induces insulin resistance, pancreatic islet hyperplasia and dysfunction in mice","volume":"6","author":"So","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.canlet.2020.11.026_bib44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.4161\/isl.2.4.12402","article-title":"FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model","volume":"2","author":"Uonaga","year":"2010","journal-title":"Islets"},{"key":"10.1016\/j.canlet.2020.11.026_bib45","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1016\/j.bpj.2012.10.028","article-title":"Autofluorescence imaging of living pancreatic islets reveals fibroblast growth factor-21 (FGF21)-induced metabolism","volume":"103","author":"Sun","year":"2012","journal-title":"Biophys. J."},{"key":"10.1016\/j.canlet.2020.11.026_bib46","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1042\/CS20190093","article-title":"Fibroblast growth factor 21 protects against lipotoxicity-induced pancreatic beta-cell dysfunction via regulation of AMPK signaling and lipid metabolism","volume":"133","author":"Xie","year":"2019","journal-title":"Clin. Sci. (Lond.)"},{"key":"10.1016\/j.canlet.2020.11.026_bib47","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.2337\/db13-0645","article-title":"High glucose represses beta-klotho expression and impairs fibroblast growth factor 21 action in mouse pancreatic islets: involvement of peroxisome proliferator-activated receptor gamma signaling","volume":"62","author":"So","year":"2013","journal-title":"Diabetes"},{"key":"10.1016\/j.canlet.2020.11.026_bib48","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/dom.12408","article-title":"Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin-induced insulin-deficient diabetic mice by restoring brown adipose tissue function","volume":"17","author":"Kim","year":"2015","journal-title":"Diabetes Obes. Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib49","series-title":"Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin resistant mouse models----Association with liver and adipose tissue effects","author":"Xu","year":"2009"},{"key":"10.1016\/j.canlet.2020.11.026_bib50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ejphar.2015.07.003","article-title":"Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes","volume":"764","author":"Andersen","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.canlet.2020.11.026_bib51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2337\/db13-0710","article-title":"Fibroblast growth factor 21 (FGF21) and glucagon-like peptide 1 contribute to diabetes resistance in glucagon receptor-deficient mice","volume":"63","author":"Omar","year":"2014","journal-title":"Diabetes"},{"key":"10.1016\/j.canlet.2020.11.026_bib52","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1053\/j.gastro.2009.07.064","article-title":"Fibroblast growth factor 21 reduces the severity of cerulein-induced pancreatitis in mice","volume":"137","author":"Johnson","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib53","doi-asserted-by":"crossref","first-page":"E916","DOI":"10.1152\/ajpendo.00559.2013","article-title":"Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1","volume":"306","author":"Johnson","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.canlet.2020.11.026_bib54","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrgastro.2011.4","article-title":"The clinical significance of pancreatic steatosis","volume":"8","author":"Smits","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.canlet.2020.11.026_bib55","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1056\/NEJM199305203282001","article-title":"Pancreatitis and the risk of pancreatic cancer. International pancreatitis study group","volume":"328","author":"Lowenfels","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib56","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/MPA.0000000000001037","article-title":"The interface of pancreatic cancer with diabetes, obesity, and inflammation: research gaps and opportunities: summary of a national institute of diabetes and digestive and kidney diseases workshop","volume":"47","author":"Abbruzzese","year":"2018","journal-title":"Pancreas"},{"key":"10.1016\/j.canlet.2020.11.026_bib57","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s12328-019-00953-3","article-title":"Pancreatic cancer and obesity: epidemiology, mechanism, and preventive strategies","volume":"12","author":"Rawla","year":"2019","journal-title":"Clin. J. Gastroenterol."},{"key":"10.1016\/j.canlet.2020.11.026_bib58","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molmet.2013.05.005","article-title":"Fibroblast growth factor 21 is not required for the antidiabetic actions of the thiazoladinediones","volume":"2","author":"Adams","year":"2013","journal-title":"Mol Metab"},{"key":"10.1016\/j.canlet.2020.11.026_bib59","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0049977","article-title":"FGF21 requires betaklotho to act in vivo","volume":"7","author":"Adams","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.canlet.2020.11.026_bib60","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0164351","article-title":"Elevated serum fibroblast growth factor 21 in humans with acute pancreatitis","volume":"11","author":"Shenoy","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.canlet.2020.11.026_bib61","doi-asserted-by":"crossref","first-page":"18913","DOI":"10.1073\/pnas.0810097105","article-title":"Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice","volume":"105","author":"Habbe","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2020.11.026_bib62","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1158\/0008-5472.CAN-11-2612","article-title":"A comprehensive survey of Ras mutations in cancer","volume":"72","author":"Prior","year":"2012","journal-title":"Canc. Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib63","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2007.01.012","article-title":"Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice","volume":"11","author":"Guerra","year":"2007","journal-title":"Canc. Cell"},{"key":"10.1016\/j.canlet.2020.11.026_bib64","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1172\/JCI59743","article-title":"An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice","volume":"122","author":"Daniluk","year":"2012","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.canlet.2020.11.026_bib65","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1053\/j.gastro.2013.08.018","article-title":"A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice","volume":"145","author":"Philip","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib66","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2019.06.002","article-title":"Fibroblast growth factor 21 ameliorates pancreatic fibrogenesis via regulating polarization of macrophages","volume":"382","author":"Wang","year":"2019","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib67","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1210\/en.2011-1909","article-title":"Role of fibroblast growth factor 21 (FGF21) in undernutrition-related attenuation of growth in mice","volume":"153","author":"Kubicky","year":"2012","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib68","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/cvr\/cvu263","article-title":"Fibroblast growth factor 21 protects the heart from oxidative stress","volume":"106","author":"Planavila","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib69","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.1210\/en.2016-1710","article-title":"FGF21-FGFR1 coordinates phospholipid homeostasis, lipid droplet function, and ER stress in obesity","volume":"157","author":"Ye","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib70","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.15252\/embj.201696179","article-title":"OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance","volume":"36","author":"Pereira","year":"2017","journal-title":"EMBO J."},{"key":"10.1016\/j.canlet.2020.11.026_bib71","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/S1474-4422(11)70155-7","article-title":"FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study","volume":"10","author":"Suomalainen","year":"2011","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.canlet.2020.11.026_bib72","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.yexcr.2016.06.020","article-title":"FGF21 represses cerebrovascular aging via improving mitochondrial biogenesis and inhibiting p53 signaling pathway in an AMPK-dependent manner","volume":"346","author":"Wang","year":"2016","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib73","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.bbrc.2018.06.130","article-title":"High expression of fibroblast growth factor-21 in liposarcoma patients indicated better prognosis and less recurrence","volume":"503","author":"Lou","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.canlet.2020.11.026_bib74","doi-asserted-by":"crossref","first-page":"112108","DOI":"10.1016\/j.yexcr.2020.112108","article-title":"FGF21 mitigates atherosclerosis via inhibition of NLRP3 inflammasome-mediated vascular endothelial cells pyroptosis","author":"Zeng","year":"2020","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib75","doi-asserted-by":"crossref","first-page":"106219","DOI":"10.1016\/j.intimp.2020.106219","article-title":"Fibroblast Growth Factor 21 dependent TLR4\/MYD88\/NF-kappaB signaling activation is involved in lipopolysaccharide-induced acute lung injury","volume":"80","author":"Gao","year":"2020","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.canlet.2020.11.026_bib76","doi-asserted-by":"crossref","first-page":"14254","DOI":"10.1096\/fj.201901347RR","article-title":"KLF15-activating Twist2 ameliorated hepatic steatosis by inhibiting inflammation and improving mitochondrial dysfunction via NF-kappaB-FGF21 or SREBP1c-FGF21 pathway","volume":"33","author":"Zhou","year":"2019","journal-title":"Faseb. J."},{"key":"10.1016\/j.canlet.2020.11.026_bib77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12950-019-0221-3","article-title":"Deficiency of fibroblast growth factor 21 aggravates obesity-induced atrophic responses in skeletal muscle","volume":"16","author":"Kim","year":"2019","journal-title":"J. Inflamm."},{"key":"10.1016\/j.canlet.2020.11.026_bib78","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.intimp.2016.05.026","article-title":"Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-kappaB signaling pathway","volume":"38","author":"Yu","year":"2016","journal-title":"Int. Immunopharm."},{"key":"10.1016\/j.canlet.2020.11.026_bib79","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fendo.2013.00194","article-title":"Stressed liver and muscle call on adipocytes with FGF21","volume":"4","author":"Luo","year":"2013","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.canlet.2020.11.026_bib80","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1471-230X-13-67","article-title":"Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress","volume":"13","author":"Yang","year":"2013","journal-title":"BMC Gastroenterol."},{"key":"10.1016\/j.canlet.2020.11.026_bib81","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1210\/en.2009-0532","article-title":"Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis","volume":"150","author":"Badman","year":"2009","journal-title":"Endocrinology"},{"key":"10.1016\/j.canlet.2020.11.026_bib82","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cmet.2012.08.002","article-title":"betaKlotho is required for fibroblast growth factor 21 effects on growth and metabolism","volume":"16","author":"Ding","year":"2012","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib83","article-title":"Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB","volume":"7","author":"Yang","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.canlet.2020.11.026_bib84","doi-asserted-by":"crossref","first-page":"29751","DOI":"10.1074\/jbc.M114.565960","article-title":"Fibroblast growth factor 21 is regulated by the IRE1alpha-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis","volume":"289","author":"Jiang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2020.11.026_bib85","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.cmet.2018.04.001","article-title":"The hormone FGF21 stimulates water drinking in response to ketogenic diet and alcohol","volume":"27","author":"Song","year":"2018","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib86","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cmet.2015.12.003","article-title":"FGF21 mediates endocrine control of simple sugar intake and sweet taste preference by the liver","volume":"23","author":"von Holstein-Rathlou","year":"2016","journal-title":"Cell Metabol."},{"key":"10.1016\/j.canlet.2020.11.026_bib87","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nm.3014","article-title":"Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine","volume":"19","author":"Kim","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.canlet.2020.11.026_bib88","doi-asserted-by":"crossref","first-page":"11592","DOI":"10.1073\/pnas.1412047111","article-title":"Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21","volume":"111","author":"Cornu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2020.11.026_bib89","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.celrep.2016.08.086","article-title":"mTORC1 is a major regulatory node in the FGF21 signaling network in adipocytes","volume":"17","author":"Minard","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.canlet.2020.11.026_bib90","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1053\/j.gastro.2013.10.059","article-title":"Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21","volume":"146","author":"Li","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib91","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1002\/hep.27719","article-title":"Activation of aryl hydrocarbon receptor dissociates fatty liver from insulin resistance by inducing fibroblast growth factor 21","volume":"61","author":"Lu","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.canlet.2020.11.026_bib92","doi-asserted-by":"crossref","first-page":"27938","DOI":"10.1038\/srep27938","article-title":"CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis","volume":"6","author":"Park","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2020.11.026_bib93","doi-asserted-by":"crossref","first-page":"9175","DOI":"10.1074\/jbc.M116.767590","article-title":"The hepatokine FGF21 is crucial for peroxisome proliferator-activated receptor-alpha agonist-induced amelioration of metabolic disorders in obese mice","volume":"292","author":"Goto","year":"2017","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2020.11.026_bib94","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tox.2017.01.016","article-title":"Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARalpha-FGF21 axis","volume":"379","author":"Chen","year":"2017","journal-title":"Toxicology"},{"key":"10.1016\/j.canlet.2020.11.026_bib95","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1093\/hmg\/ddx097","article-title":"Downregulation of pathways implicated in liver inflammation and tumorigenesis of glycogen storage disease type Ia mice receiving gene therapy","volume":"26","author":"Kim","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.canlet.2020.11.026_bib96","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/10715762.2017.1320554","article-title":"Amelioration of late-onset hepatic steatosis in IDH2-deficient mice","volume":"51","author":"Lee","year":"2017","journal-title":"Free Radic. Res."},{"key":"10.1016\/j.canlet.2020.11.026_bib97","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/s41467-017-01878-6","article-title":"Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis","volume":"8","author":"Han","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2020.11.026_bib98","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1073\/pnas.1816023116","article-title":"Hepatic posttranscriptional network comprised of CCR4-NOT deadenylase and FGF21 maintains systemic metabolic homeostasis","volume":"116","author":"Morita","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2020.11.026_bib99","doi-asserted-by":"crossref","first-page":"15184","DOI":"10.1073\/pnas.1904360116","article-title":"YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity","volume":"116","author":"Wang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.canlet.2020.11.026_bib100","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41467-020-14384-z","article-title":"Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase","volume":"11","author":"Byun","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2020.11.026_bib101","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1053\/j.gastro.2010.04.054","article-title":"Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease","volume":"139","author":"Dushay","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib102","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1210\/jc.2013-1250","article-title":"Circulating levels of FGF-21 in obese youth: associations with liver fat content and markers of liver damage","volume":"98","author":"Giannini","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.canlet.2020.11.026_bib103","doi-asserted-by":"crossref","unstructured":"H. Li, Q. Fang, F. Gao, J. Fan, J. Zhou, X. Wang, H. Zhang, X. Pan, Y. Bao, K. Xiang, A. Xu, W. Jia, Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride, J. Hepatol., 53 934-940.","DOI":"10.1016\/j.jhep.2010.05.018"},{"key":"10.1016\/j.canlet.2020.11.026_bib104","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1530\/EJE-11-0783","article-title":"Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat","volume":"166","author":"Matikainen","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.canlet.2020.11.026_bib105","doi-asserted-by":"crossref","unstructured":"Y. Yilmaz, F. Eren, O. Yonal, R. Kurt, B. Aktas, C.A. Celikel, O. Ozdogan, N. Imeryuz, C. Kalayci, E. Avsar, Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease, Eur. J. Clin. Invest., 40 887-892.","DOI":"10.1111\/j.1365-2362.2010.02338.x"},{"key":"10.1016\/j.canlet.2020.11.026_bib106","first-page":"1762","article-title":"Loss of FGF21 in diabetic mouse during hepatocellular carcinogenetic transformation","volume":"5","author":"Zhang","year":"2015","journal-title":"Am J Cancer Res"},{"key":"10.1016\/j.canlet.2020.11.026_bib107","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1053\/j.gastro.2014.07.044","article-title":"Fibroblast growth factor 21 limits lipotoxicity by promoting hepatic fatty acid activation in mice on methionine and choline-deficient diets","volume":"147","author":"Fisher","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.canlet.2020.11.026_bib108","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00125-014-3475-6","article-title":"Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress","volume":"58","author":"Kim","year":"2015","journal-title":"Diabetologia"},{"key":"10.1016\/j.canlet.2020.11.026_bib109","first-page":"1011","article-title":"Lack of fibroblast growth factor 21 accelerates metabolic liver injury characterized by steatohepatities in mice","volume":"6","author":"Liu","year":"2016","journal-title":"Am J Cancer Res"},{"key":"10.1016\/j.canlet.2020.11.026_bib110","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/oby.22344","article-title":"Pegbelfermin (BMS-986036), PEGylated FGF21, in patients with obesity and type 2 diabetes: results from a randomized phase 2 study","volume":"27","author":"Charles","year":"2019","journal-title":"Obesity"},{"key":"10.1016\/j.canlet.2020.11.026_bib111","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.molmet.2018.03.010","article-title":"FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest","volume":"11","author":"Soberg","year":"2018","journal-title":"Mol Metab"}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030438352030625X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030438352030625X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:04:09Z","timestamp":1777550649000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S030438352030625X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":111,"alternative-id":["S030438352030625X"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2020.11.026","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"FGF21 in obesity and cancer: New insights","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2020.11.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}