{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:07:31Z","timestamp":1792292851351,"version":"4.4.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T00:00:00Z","timestamp":1644105600000},"content-version":"am","delay-in-days":342,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2016-67017-24431"],"award-info":[{"award-number":["2016-67017-24431"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["A1341"],"award-info":[{"award-number":["A1341"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical and Biophysical Research Communications"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.bbrc.2021.01.070","type":"journal-article","created":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T15:45:36Z","timestamp":1612626336000},"page":"183-188","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["mTORC1 silencing during intestinal epithelial Caco-2\u00a0cell differentiation is mediated by the activation of the AMPK\/TSC2 pathway"],"prefix":"10.1016","volume":"545","author":[{"given":"Harleen","family":"Kaur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0532-9887","authenticated-orcid":false,"given":"R\u00e9gis","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbrc.2021.01.070_bib1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/15384101.2015.1120925","article-title":"Coordinating cell proliferation and differentiation: antagonism between cell cycle regulators and cell type-specific gene expression","volume":"15","author":"Ruijtenberg","year":"2016","journal-title":"Cell Cycle"},{"key":"10.1016\/j.bbrc.2021.01.070_bib2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev.physiol.010908.163145","article-title":"Stem cells, self-renewal, and differentiation in the intestinal epithelium","volume":"71","author":"van der Flier","year":"2009","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib3","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1007\/s00018-019-03085-6","article-title":"Role of mTORC1 in intestinal epithelial repair and tumorigenesis","volume":"76","author":"Kaur","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.bbrc.2021.01.070_bib4","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2353\/ajpath.2010.090622","article-title":"A\u00a0novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis","volume":"176","author":"Deng","year":"2010","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cell.2012.12.012","article-title":"Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties","volume":"152","author":"Schwitalla","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.bbrc.2021.01.070_bib6","first-page":"767","article-title":"mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice","volume":"123","author":"Thiem","year":"2013","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.bbrc.2021.01.070_bib7","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.588","article-title":"TSC2\/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium","volume":"6","author":"Zhou","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.bbrc.2021.01.070_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180853","article-title":"Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation","volume":"12","author":"Buerger","year":"2017","journal-title":"PloS One"},{"key":"10.1016\/j.bbrc.2021.01.070_bib9","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.3389\/fimmu.2018.02786","article-title":"Epidermal mTORC1 signaling contributes to the pathogenesis of psoriasis and could serve as a therapeutic target","volume":"9","author":"Buerger","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2002417","article-title":"The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile","volume":"16","author":"Lyons","year":"2018","journal-title":"PLoS Biol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s42003-018-0028-4","article-title":"mTORC1 impedes osteoclast differentiation via calcineurin and NFATc1","volume":"1","author":"Huynh","year":"2018","journal-title":"Commun Biol"},{"key":"10.1016\/j.bbrc.2021.01.070_bib12","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/s41385-018-0018-3","article-title":"Colonic epithelial mTORC1 promotes ulcerative colitis through COX-2-mediated Th17 responses","volume":"11","author":"Lin","year":"2018","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib13","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The tuberous sclerosis complex","volume":"355","author":"Crino","year":"2006","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.bbrc.2021.01.070_bib14","doi-asserted-by":"crossref","first-page":"25227","DOI":"10.1074\/jbc.M114.554881","article-title":"Akt-dependent activation of mTORC1 complex involves phosphorylation of mTOR (mammalian target of rapamycin) by IkappaB kinase alpha (IKKalpha)","volume":"289","author":"Dan","year":"2014","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.bbrc.2021.01.070_bib15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng1494","article-title":"Dysregulation of the TSC-mTOR pathway in human disease","volume":"37","author":"Inoki","year":"2005","journal-title":"Nat. Genet."},{"key":"10.1016\/j.bbrc.2021.01.070_bib16","doi-asserted-by":"crossref","first-page":"R251","DOI":"10.1093\/hmg\/ddi260","article-title":"Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways","volume":"2","author":"Kwiatkowski","year":"2005","journal-title":"Hum Mol Genet 14 Spec No"},{"key":"10.1016\/j.bbrc.2021.01.070_bib17","doi-asserted-by":"crossref","first-page":"32493","DOI":"10.1074\/jbc.C300226200","article-title":"Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner","volume":"278","author":"Castro","year":"2003","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.bbrc.2021.01.070_bib18","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1097-2765(03)00220-X","article-title":"Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E-BP signaling, is inhibited by TSC1 and 2","volume":"11","author":"Garami","year":"2003","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bbrc.2021.01.070_bib19","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","article-title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins","volume":"5","author":"Zhang","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib20","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.molcel.2007.03.003","article-title":"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase","volume":"25","author":"Sancak","year":"2007","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bbrc.2021.01.070_bib21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cellsig.2011.08.010","article-title":"Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k\/Akt signaling pathway","volume":"24","author":"Wang","year":"2012","journal-title":"Cell. Signal."},{"key":"10.1016\/j.bbrc.2021.01.070_bib22","doi-asserted-by":"crossref","first-page":"69076","DOI":"10.18632\/oncotarget.17299","article-title":"PRAS40 signaling in tumor","volume":"8","author":"Lv","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.bbrc.2021.01.070_bib23","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.588","article-title":"TSC2\/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium","volume":"6","author":"Zhou","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.bbrc.2021.01.070_bib24","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1101\/gad.1110003","article-title":"Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling","volume":"17","author":"Inoki","year":"2003","journal-title":"Genes Dev."},{"key":"10.1016\/j.bbrc.2021.01.070_bib25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 complex: a molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"10.1016\/j.bbrc.2021.01.070_bib26","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival","volume":"115","author":"Inoki","year":"2003","journal-title":"Cell"},{"key":"10.1016\/j.bbrc.2021.01.070_bib28","doi-asserted-by":"crossref","DOI":"10.1038\/srep13828","article-title":"TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1","volume":"5","author":"Plescher","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bbrc.2021.01.070_bib29","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cmet.2020.01.015","article-title":"AMPK and TOR: the yin and yang of cellular nutrient sensing and growth control","volume":"31","author":"Gonzalez","year":"2020","journal-title":"Cell Metabol."},{"key":"10.1016\/j.bbrc.2021.01.070_bib30","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/2211-5463.12195","article-title":"TSC2\/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts","volume":"7","author":"Miyazaki","year":"2017","journal-title":"FEBS Open Bio"},{"key":"10.1016\/j.bbrc.2021.01.070_bib31","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol. Cell"},{"key":"10.1016\/j.bbrc.2021.01.070_bib32","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.3390\/ijms19072040","article-title":"Implications of AMPK in the formation of epithelial tight junctions","volume":"19","author":"Rowart","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bbrc.2021.01.070_bib33","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/cdd.2017.14","article-title":"AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression","volume":"24","author":"Sun","year":"2017","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.bbrc.2021.01.070_bib34","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1080\/09168451.2014.951027","article-title":"Theaflavins enhance intestinal barrier of Caco-2 Cell monolayers through the expression of AMP-activated protein kinase-mediated Occludin, Claudin-1, and ZO-1","volume":"79","author":"Park","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"10.1016\/j.bbrc.2021.01.070_bib35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.isci.2018.06.006","article-title":"Serine phosphorylation by mTORC1 promotes IRS-1 degradation through SCFbeta-TRCP E3 ubiquitin ligase","volume":"5","author":"Yoneyama","year":"2018","journal-title":"iScience"},{"key":"10.1016\/j.bbrc.2021.01.070_bib36","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1158\/2159-8290.CD-11-0085","article-title":"mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling","volume":"1","author":"Rodrik-Outmezguine","year":"2011","journal-title":"Canc. Discov."}],"container-title":["Biochemical and Biophysical Research Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X21001212?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006291X21001212?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:12:17Z","timestamp":1777392737000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006291X21001212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":36,"alternative-id":["S0006291X21001212"],"URL":"https:\/\/doi.org\/10.1016\/j.bbrc.2021.01.070","relation":{},"ISSN":["0006-291X"],"issn-type":[{"value":"0006-291X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"mTORC1 silencing during intestinal epithelial Caco-2\u00a0cell differentiation is mediated by the activation of the AMPK\/TSC2 pathway","name":"articletitle","label":"Article Title"},{"value":"Biochemical and Biophysical Research Communications","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbrc.2021.01.070","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}