SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling

Menno J. Oudhoff; Mitchell J.S. Braam; Spencer A. Freeman; Denise Wong; David G. Rattray; Jia Wang; Frann Antignano; Kimberly Snyder; Ido Refaeli; Michael R. Hughes; Kelly M. McNagny; Michael R. Gold; Cheryl H. Arrowsmith; Toshiro Sato; Fabio M.V. Rossi; John H. Tatlock; Dafydd R. Owen; Peter J. Brown; Colby Zaph

doi:10.1016/j.devcel.2016.03.002

SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling

Menno J. Oudhoff
, Mitchell J.S. Braam
, Spencer A. Freeman
, Denise Wong
, David G. Rattray
, Jia Wang
, Frann Antignano
, Kimberly Snyder
, Ido Refaeli
, Michael R. Hughes
, Kelly M. McNagny
, Michael R. Gold
, Cheryl H. Arrowsmith
, Toshiro Sato
, Fabio M.V. Rossi
, John H. Tatlock
, Dafydd R. Owen
, Peter J. Brown
, Colby Zaph

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

109 Citations (Scopus)

Abstract

Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

Original language	English
Pages (from-to)	47-57
Number of pages	11
Journal	Developmental Cell
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/j.devcel.2016.03.002
Publication status	Published - 4 Apr 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.devcel.2016.03.002

3623670-oaFinal published version, 2.95 MB

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Oudhoff, M. J., Braam, M. J. S., Freeman, S. A., Wong, D., Rattray, D. G., Wang, J., Antignano, F., Snyder, K., Refaeli, I., Hughes, M. R., McNagny, K. M., Gold, M. R., Arrowsmith, C. H., Sato, T., Rossi, F. M. V., Tatlock, J. H., Owen, D. R., Brown, P. J., & Zaph, C. (2016). SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling. Developmental Cell, 37(1), 47-57. https://doi.org/10.1016/j.devcel.2016.03.002

@article{c502820c40f8469d902f877e977a5be4,

title = "SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling",

abstract = "Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.",

author = "Oudhoff, \{Menno J.\} and Braam, \{Mitchell J.S.\} and Freeman, \{Spencer A.\} and Denise Wong and Rattray, \{David G.\} and Jia Wang and Frann Antignano and Kimberly Snyder and Ido Refaeli and Hughes, \{Michael R.\} and McNagny, \{Kelly M.\} and Gold, \{Michael R.\} and Arrowsmith, \{Cheryl H.\} and Toshiro Sato and Rossi, \{Fabio M.V.\} and Tatlock, \{John H.\} and Owen, \{Dafydd R.\} and Brown, \{Peter J.\} and Colby Zaph",

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doi = "10.1016/j.devcel.2016.03.002",

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Oudhoff, MJ, Braam, MJS, Freeman, SA, Wong, D, Rattray, DG, Wang, J, Antignano, F, Snyder, K, Refaeli, I, Hughes, MR, McNagny, KM, Gold, MR, Arrowsmith, CH, Sato, T, Rossi, FMV, Tatlock, JH, Owen, DR, Brown, PJ & Zaph, C 2016, 'SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling', Developmental Cell, vol. 37, no. 1, pp. 47-57. https://doi.org/10.1016/j.devcel.2016.03.002

TY - JOUR

T1 - SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling

AU - Oudhoff, Menno J.

AU - Braam, Mitchell J.S.

AU - Freeman, Spencer A.

AU - Wong, Denise

AU - Rattray, David G.

AU - Wang, Jia

AU - Antignano, Frann

AU - Snyder, Kimberly

AU - Refaeli, Ido

AU - Hughes, Michael R.

AU - McNagny, Kelly M.

AU - Gold, Michael R.

AU - Arrowsmith, Cheryl H.

AU - Sato, Toshiro

AU - Rossi, Fabio M.V.

AU - Tatlock, John H.

AU - Owen, Dafydd R.

AU - Brown, Peter J.

AU - Zaph, Colby

PY - 2016/4/4

Y1 - 2016/4/4

N2 - Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

AB - Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

UR - http://www.ncbi.nlm.nih.gov/pubmed/27046831

U2 - 10.1016/j.devcel.2016.03.002

DO - 10.1016/j.devcel.2016.03.002

M3 - Article

SN - 1534-5807

VL - 37

SP - 47

EP - 57

JO - Developmental Cell

JF - Developmental Cell

IS - 1

ER -

SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling

Abstract

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SETD7-dependent regulation of Hippo/YAP and Wnt/beta-catenin pathways in the intestine

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SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/β-Catenin and Hippo/YAP signaling

Abstract

UN SDGs

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SETD7-dependent regulation of Hippo/YAP and Wnt/beta-catenin pathways in the intestine

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