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 › Academic › peer-review

4 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 - 7 Jun 2021

Bibliographical note

Funding Information:
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.

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

Access to Document

10.1038/s41467-021-23641-8

Cite this

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), [3354]. https://doi.org/10.1038/s41467-021-23641-8

@article{09097c1c5ff24a6c97f39fbeba031e13,

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.",

author = "Janmaat, {Vincent T.} and Kateryna Nesteruk and Spaander, {Manon C.W.} and Verhaar, {Auke P.} and Bingting Yu and Silva, {Rodrigo A.} and Phillips, {Wayne A.} and Marcin Magierowski and {van de Winkel}, Anouk and Stadler, {H. Scott} and Tatiana Sandoval-Guzm{\'a}n and {van der Laan}, {Luc J.W.} and Kuipers, {Ernst J.} and Ron Smits and Bruno, {Marco J.} and Fuhler, {Gwenny M.} and Clemons, {Nicholas J.} and Peppelenbosch, {Maikel P.}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jun,

day = "7",

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

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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

TY - JOUR

T1 - HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

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.

N1 - Funding Information: 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. Publisher Copyright: © 2021, The Author(s).

PY - 2021/6/7

Y1 - 2021/6/7

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.

UR - http://www.scopus.com/inward/record.url?scp=85107557444&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-23641-8

DO - 10.1038/s41467-021-23641-8

M3 - Article

C2 - 34099670

AN - SCOPUS:85107557444

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3354

ER -

HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this