PMID- 20708588
OWN - NLM
STAT- MEDLINE
DCOM- 20100913
LR  - 20240210
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 19
IP  - 2
DP  - 2010 Aug 17
TI  - Focal adhesion kinase is required for intestinal regeneration and tumorigenesis 
      downstream of Wnt/c-Myc signaling.
PG  - 259-69
LID - 10.1016/j.devcel.2010.07.015 [doi]
AB  - The intestinal epithelium has a remarkable capacity to regenerate after injury 
      and DNA damage. Here, we show that the integrin effector protein Focal Adhesion 
      Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage 
      signaling, but is essential for intestinal regeneration following DNA damage. 
      Given Wnt/c-Myc signaling is activated following intestinal regeneration, we 
      investigated the functional importance of FAK following deletion of the Apc tumor 
      suppressor protein within the intestinal epithelium. Following Apc loss, FAK 
      expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak 
      strongly reduced proliferation normally induced following Apc loss, and this was 
      associated with reduced levels of phospho-Akt and suppression of intestinal 
      tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt 
      Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. 
      Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in 
      patients at high risk of developing colorectal cancer.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Ashton, Gabrielle H
AU  - Ashton GH
AD  - The Beatson Institute for Cancer Research, Glasgow, UK.
FAU - Morton, Jennifer P
AU  - Morton JP
FAU - Myant, Kevin
AU  - Myant K
FAU - Phesse, Toby J
AU  - Phesse TJ
FAU - Ridgway, Rachel A
AU  - Ridgway RA
FAU - Marsh, Victoria
AU  - Marsh V
FAU - Wilkins, Julie A
AU  - Wilkins JA
FAU - Athineos, Dimitris
AU  - Athineos D
FAU - Muncan, Vanesa
AU  - Muncan V
FAU - Kemp, Richard
AU  - Kemp R
FAU - Neufeld, Kristi
AU  - Neufeld K
FAU - Clevers, Hans
AU  - Clevers H
FAU - Brunton, Valerie
AU  - Brunton V
FAU - Winton, Douglas J
AU  - Winton DJ
FAU - Wang, Xiaoyan
AU  - Wang X
FAU - Sears, Rosalie C
AU  - Sears RC
FAU - Clarke, Alan R
AU  - Clarke AR
FAU - Frame, Margaret C
AU  - Frame MC
FAU - Sansom, Owen J
AU  - Sansom OJ
LA  - eng
GR  - C157/A9148/CRUK_/Cancer Research UK/United Kingdom
GR  - 12481/CRUK_/Cancer Research UK/United Kingdom
GR  - R01 CA129040-01A2/CA/NCI NIH HHS/United States
GR  - 10-0643/AICR_/Worldwide Cancer Research/United Kingdom
GR  - R01 CA129040/CA/NCI NIH HHS/United States
GR  - C1295/A9590/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Wnt Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Dev Cell. 2010 Aug 17;19(2):185-6. PMID: 20708578
MH  - Animals
MH  - Focal Adhesion Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Humans
MH  - Intestinal Neoplasms/*metabolism/pathology
MH  - Intestines/pathology/*physiology
MH  - Intracellular Signaling Peptides and Proteins/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Proto-Oncogene Proteins c-myc/genetics/*metabolism
MH  - *Regeneration
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
MH  - Wnt Proteins/genetics/*metabolism
PMC - PMC3291717
MID - NIHMS354171
EDAT- 2010/08/17 06:00
MHDA- 2010/09/14 06:00
PMCR- 2012/03/02
CRDT- 2010/08/17 06:00
PHST- 2008/03/30 00:00 [received]
PHST- 2010/01/07 00:00 [revised]
PHST- 2010/06/16 00:00 [accepted]
PHST- 2010/08/17 06:00 [entrez]
PHST- 2010/08/17 06:00 [pubmed]
PHST- 2010/09/14 06:00 [medline]
PHST- 2012/03/02 00:00 [pmc-release]
AID - S1534-5807(10)00343-6 [pii]
AID - 10.1016/j.devcel.2010.07.015 [doi]
PST - ppublish
SO  - Dev Cell. 2010 Aug 17;19(2):259-69. doi: 10.1016/j.devcel.2010.07.015.