PMID- 22464327
OWN - NLM
STAT- MEDLINE
DCOM- 20120604
LR  - 20220318
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 149
IP  - 1
DP  - 2012 Mar 30
TI  - The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that 
      functions as a tumor suppressor.
PG  - 146-58
LID - 10.1016/j.cell.2012.02.042 [doi]
AB  - Lineage mapping has identified both proliferative and quiescent intestinal stem 
      cells, but the molecular circuitry controlling stem cell quiescence is 
      incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor, 
      marks predominately noncycling, long-lived stem cells that are located at the 
      crypt base and that, upon injury, proliferate and divide to replenish damaged 
      crypts. Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly 
      from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes 
      upregulated in the Lrig1(+) population include those involved in cell cycle 
      repression and response to oxidative damage. Loss of Apc in Lrig1(+) cells leads 
      to intestinal adenomas, and genetic ablation of Lrig1 results in heightened 
      ErbB1-3 expression and duodenal adenomas. These results shed light on the 
      relationship between proliferative and quiescent intestinal stem cells and 
      support a model in which intestinal stem cell quiescence is maintained by 
      calibrated ErbB signaling with loss of a negative regulator predisposing to 
      neoplasia.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Powell, Anne E
AU  - Powell AE
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 
      37232, USA.
FAU - Wang, Yang
AU  - Wang Y
FAU - Li, Yina
AU  - Li Y
FAU - Poulin, Emily J
AU  - Poulin EJ
FAU - Means, Anna L
AU  - Means AL
FAU - Washington, Mary K
AU  - Washington MK
FAU - Higginbotham, James N
AU  - Higginbotham JN
FAU - Juchheim, Alwin
AU  - Juchheim A
FAU - Prasad, Nripesh
AU  - Prasad N
FAU - Levy, Shawn E
AU  - Levy SE
FAU - Guo, Yan
AU  - Guo Y
FAU - Shyr, Yu
AU  - Shyr Y
FAU - Aronow, Bruce J
AU  - Aronow BJ
FAU - Haigis, Kevin M
AU  - Haigis KM
FAU - Franklin, Jeffrey L
AU  - Franklin JL
FAU - Coffey, Robert J
AU  - Coffey RJ
LA  - eng
SI  - GEO/GSE5206
GR  - CA46413/CA/NCI NIH HHS/United States
GR  - P50CA095103/CA/NCI NIH HHS/United States
GR  - P50 CA095103/CA/NCI NIH HHS/United States
GR  - R01 CA046413/CA/NCI NIH HHS/United States
GR  - P30 DK043351/DK/NIDDK NIH HHS/United States
GR  - CA151566/CA/NCI NIH HHS/United States
GR  - R01 CA151566/CA/NCI NIH HHS/United States
GR  - U01 CA084239/CA/NCI NIH HHS/United States
GR  - U01CA084239/CA/NCI NIH HHS/United States
GR  - T32 GM008554/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000077/TR/NCATS NIH HHS/United States
GR  - T32GM008554/GM/NIGMS NIH HHS/United States
GR  - T32 CA119925/CA/NCI NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - T32CA119925/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (LRIG1 protein, human)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (Lrig1 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
CIN - Nat Rev Cancer. 2012 May 24;12(5):318. doi: 10.1038/nrc3268. PMID: 22525573
MH  - Adenoma/pathology
MH  - Adenomatous Polyposis Coli Protein/metabolism
MH  - Animals
MH  - Colon/cytology/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Gene Expression Profiling
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Intestinal Neoplasms/pathology
MH  - Intestine, Small/cytology/*metabolism
MH  - Membrane Glycoproteins/*metabolism
MH  - Mice
MH  - Nerve Tissue Proteins/*metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Signal Transduction
MH  - Stem Cells/cytology/metabolism
PMC - PMC3563328
MID - NIHMS410909
EDAT- 2012/04/03 06:00
MHDA- 2012/06/05 06:00
PMCR- 2013/03/30
CRDT- 2012/04/03 06:00
PHST- 2011/06/30 00:00 [received]
PHST- 2012/01/12 00:00 [revised]
PHST- 2012/02/01 00:00 [accepted]
PHST- 2012/04/03 06:00 [entrez]
PHST- 2012/04/03 06:00 [pubmed]
PHST- 2012/06/05 06:00 [medline]
PHST- 2013/03/30 00:00 [pmc-release]
AID - S0092-8674(12)00280-2 [pii]
AID - 10.1016/j.cell.2012.02.042 [doi]
PST - ppublish
SO  - Cell. 2012 Mar 30;149(1):146-58. doi: 10.1016/j.cell.2012.02.042.