Journal article

HOXA13 in etiology and oncogenic potential of Barrett's esophagus

Vincent T Janmaat, Kateryna Nesteruk, Manon CW Spaander, Auke P Verhaar, Bingting Yu, Rodrigo A Silva, Wayne A Phillips, Marcin Magierowski, Anouk van de Winkel, H Scott Stadler, Tatiana Sandoval-Guzman, Luc JW van der Laan, Ernst J Kuipers, Ron Smits, Marco J Bruno, Gwenny M Fuhler, Nicholas J Clemons, Maikel P Peppelenbosch

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2021

Abstract

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 f..

View full abstract

Grants

Awarded by FAPESP


Awarded by National Science Centre (Poland)


Funding Acknowledgements

We would like to acknowledge H.F.B.M. Sleddens, H. Stoop, M.H.W. van Dullemen, P. Vasic, I.T.A. Edelijn, M.J. van der Lee, P.J. Zwalua, W.W. van Dam, E. Zielhuis, J. Knoop, M. Doukas, A.L. Nigg and T.P.P. van den Bosch, Erasmus MC -University Medical Center Rotterdam, for their involvement in investigation, W.N.M. Dinjens for providing material, and F. McKeon, The Jackson Laboratory for Genomic Medicine, for conceptualization and providing resources. FAPESP n. 2016/01139-0; 2017/01046-5 for funding.M.Magierowski was supported by a grant from National Science Centre (Poland): UMO-2016/23/D/NZ4/01913.