{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:14:38Z","timestamp":1790694878549,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Barrett\u2019s esophagus (BE) is a premalignant lesion that can develop into esophageal adenocarcinoma (EAC). The development of Barrett\u2019s esophagus is caused by biliary reflux, which causes extensive mutagenesis in the stem cells of the epithelium in the distal esophagus and gastro-esophageal junction. Other possible cellular origins of BE include the stem cells of the mucosal esophageal glands and their ducts, the stem cells of the stomach, residual embryonic cells and circulating bone marrow stem cells. The classical concept of healing a caustic lesion has been replaced by the concept of a cytokine storm, which forms an inflammatory microenvironment eliciting a phenotypic shift toward intestinal metaplasia of the distal esophagus. This review describes the roles of the NOTCH, hedgehog, NF-\u03baB and IL6\/STAT3 molecular pathways in the pathogenesis of BE and EAC.<\/jats:p>","DOI":"10.3390\/ijms24119304","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:19:37Z","timestamp":1685204377000},"page":"9304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Signaling Pathways in the Pathogenesis of Barrett\u2019s Esophagus and Esophageal Adenocarcinoma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8083-9428","authenticated-orcid":false,"given":"Ksenia","family":"Maslenkina","sequence":"first","affiliation":[{"name":"A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2052-914X","authenticated-orcid":false,"given":"Liudmila","family":"Mikhaleva","sequence":"additional","affiliation":[{"name":"A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Naumenko","sequence":"additional","affiliation":[{"name":"A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rositsa","family":"Vandysheva","sequence":"additional","affiliation":[{"name":"A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-8561","authenticated-orcid":false,"given":"Michail","family":"Gushchin","sequence":"additional","affiliation":[{"name":"A.P. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-4556","authenticated-orcid":false,"given":"Dmitri","family":"Atiakshin","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Centre for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia Named after Patrice Lumumba, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-7483","authenticated-orcid":false,"given":"Igor","family":"Buchwalow","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Centre for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia Named after Patrice Lumumba, 117198 Moscow, Russia"},{"name":"Institute for Hematopathology, Fangdieckstr. 75a, 22547 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Tiemann","sequence":"additional","affiliation":[{"name":"Institute for Hematopathology, Fangdieckstr. 75a, 22547 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1136\/gutjnl-2011-301174","article-title":"Barrett\u2019s metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor","volume":"61","author":"Nicholson","year":"2012","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00428-018-2317-1","article-title":"The metaplastic mosaic of Barrett\u2019s oesophagus","volume":"472","author":"Biswas","year":"2018","journal-title":"Virchows Arch."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-319-41388-4_3","article-title":"The Complex, Clonal, and Controversial Nature of Barrett\u2019s Esophagus","volume":"908","author":"Evans","year":"2016","journal-title":"Adv. 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