HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

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

doi:10.1038/s41467-021-23641-8

HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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 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.

Original language	English
Article number	3354
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23641-8
Publication status	Published - Dec 1 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Janmaat, V. T., Nesteruk, K., Spaander, M. C. W., Verhaar, A. P., Yu, B., Silva, R. A., Phillips, W. A., Magierowski, M., van de Winkel, A., Stadler, H. S., Sandoval-Guzmán, T., van der Laan, L. J. W., Kuipers, E. J., Smits, R., Bruno, M. J., Fuhler, G. M., Clemons, N. J., & Peppelenbosch, M. P. (2021). HOXA13 in etiology and oncogenic potential of Barrett’s esophagus. Nature Communications, 12(1), Article 3354. https://doi.org/10.1038/s41467-021-23641-8

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title = "HOXA13 in etiology and oncogenic potential of Barrett{\textquoteright}s esophagus",

abstract = "Barrett{\textquoteright}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{\textquoteright}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{\textquoteright}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{\textquoteright}s esophagus. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett{\textquoteright}s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury.",

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year = "2021",

month = dec,

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doi = "10.1038/s41467-021-23641-8",

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Janmaat, VT, Nesteruk, K, Spaander, MCW, Verhaar, AP, Yu, B, Silva, RA, Phillips, WA, Magierowski, M, van de Winkel, A, Stadler, HS, Sandoval-Guzmán, T, van der Laan, LJW, Kuipers, EJ, Smits, R, Bruno, MJ, Fuhler, GM, Clemons, NJ & Peppelenbosch, MP 2021, 'HOXA13 in etiology and oncogenic potential of Barrett’s esophagus', Nature Communications, vol. 12, no. 1, 3354. https://doi.org/10.1038/s41467-021-23641-8

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AU - Janmaat, Vincent T.

AU - Nesteruk, Kateryna

AU - Spaander, Manon C.W.

AU - Verhaar, Auke P.

AU - Yu, Bingting

AU - Silva, Rodrigo A.

AU - Phillips, Wayne A.

AU - Magierowski, Marcin

AU - van de Winkel, Anouk

AU - Stadler, H. Scott

AU - Sandoval-Guzmán, Tatiana

AU - van der Laan, Luc J.W.

AU - Kuipers, Ernst J.

AU - Smits, Ron

AU - Bruno, Marco J.

AU - Fuhler, Gwenny M.

AU - Clemons, Nicholas J.

AU - Peppelenbosch, Maikel P.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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