The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program

Jing Cai, Nailing Zhang, Yonggang Zheng, Roeland F. De Wilde, Anirban Maitra, Duojia Pan

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.

Original languageEnglish (US)
Pages (from-to)2383-2388
Number of pages6
JournalGenes and Development
Volume24
Issue number21
DOIs
StatePublished - Nov 1 2010

Fingerprint

Regeneration
Dextran Sulfate
Proteins
Organ Size
Oncogene Proteins
Polyps
Homeostasis

Keywords

  • Cancer
  • Growth control
  • Hippo signaling
  • Mouse
  • Regeneration

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. / Cai, Jing; Zhang, Nailing; Zheng, Yonggang; De Wilde, Roeland F.; Maitra, Anirban; Pan, Duojia.

In: Genes and Development, Vol. 24, No. 21, 01.11.2010, p. 2383-2388.

Research output: Contribution to journalArticle

Cai, Jing ; Zhang, Nailing ; Zheng, Yonggang ; De Wilde, Roeland F. ; Maitra, Anirban ; Pan, Duojia. / The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. In: Genes and Development. 2010 ; Vol. 24, No. 21. pp. 2383-2388.
@article{c39addf37c0b4dcbbff79279140f519f,
title = "The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program",
abstract = "Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.",
keywords = "Cancer, Growth control, Hippo signaling, Mouse, Regeneration",
author = "Jing Cai and Nailing Zhang and Yonggang Zheng and {De Wilde}, {Roeland F.} and Anirban Maitra and Duojia Pan",
year = "2010",
month = "11",
day = "1",
doi = "10.1101/gad.1978810",
language = "English (US)",
volume = "24",
pages = "2383--2388",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "21",

}

TY - JOUR

T1 - The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program

AU - Cai, Jing

AU - Zhang, Nailing

AU - Zheng, Yonggang

AU - De Wilde, Roeland F.

AU - Maitra, Anirban

AU - Pan, Duojia

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.

AB - Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.

KW - Cancer

KW - Growth control

KW - Hippo signaling

KW - Mouse

KW - Regeneration

UR - http://www.scopus.com/inward/record.url?scp=78049451932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049451932&partnerID=8YFLogxK

U2 - 10.1101/gad.1978810

DO - 10.1101/gad.1978810

M3 - Article

C2 - 21041407

AN - SCOPUS:78049451932

VL - 24

SP - 2383

EP - 2388

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 21

ER -