OXA13 in etiology and oncogenic potential of Barrett's esophagu

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Janmaat, Vincent T. ^[1] ; Nesteruk, Kateryna ^[1] ; Spaander, Manon C. W. ^[1] ; Verhaar, Auke P. ^[1] ; Yu, Bingting ^[1] ; Silva, Rodrigo A. ^[1] ; Phillips, Wayne A. ^{[2, 3, 4]} ; Magierowski, Marcin ^{[1, 5]} ; van de Winkel, Anouk ^[1] ; Stadler, H. Scott ^[6] ; Sandoval-Guzman, Tatiana ^[7] ; van der Laan, Luc J. W. ^[8] ; Kuipers, Ernst J. ^[1] ; Smits, Ron ^[1] ; Bruno, Marco J. ^[1] ; Fuhler, Gwenny M. ^[1] ; Clemons, Nicholas J. ^{[2, 4]} ; Peppelenbosch, Maikel P. ^[1]

Afiliação do(s) autor(es)

^[1] Erasmus MC Univ Med Ctr Rotterdam, Dept Gastroenterol & Hepatol, Rotterdam - Netherlands

^[2] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic - Australia

^[3] Univ Melbourne, Dept Surg, St Vincents Hosp, Melbourne, Vic - Australia

^[4] Peter MacCallum Canc Ctr, Div Canc Res, Melbourne, Vic - Australia

^[5] Jagiellonian Univ Med Coll, Fac Med, Dept Physiol, Krakow - Poland

^[6] Shriners Hosp Children, Dept Skeletal Biol, Portland, OR - USA

^[7] Tech Univ Dresden, DFG Ctr Regenerat Therapies, Dresden - Germany

^[8] Erasmus MC Univ Med Ctr Rotterdam, Dept Surg, Rotterdam - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 12, n. 1 JUN 7 2021.
• Citações Web of Science: 0

Resumo

Barrett's esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett's esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett's esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in Barrett's esophagus. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett's esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury. Barrett's esophagus is a pro-oncogenic lesion in the proximal gastrointestinal tract, but with a distal colon-like morphology. Here the authors report that the distal HOX gene HOXA13 is expressed in Barrett's esophagus and in single cells of the physiological esophagus, and may underlie the phenotypic aspects of metaplasia and increase proliferation. (AU)

• Processo FAPESP: 16/01139-0 - Regulação epigenética mediada por fatores parácrinos produzidos por células endoteliais em células osteoblásticas
• Beneficiário: Rodrigo Augusto da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/01046-5 - Transcriptoma e metiloma de células osteoblástica em reposta a efeitos parácrinos de células endoteliais sob modelos estático e dinâmico.
• Beneficiário: Rodrigo Augusto da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado