The pan-ErbB negative regulator, Lrig1, is an intestinal stem cell marker that functions as a tumor suppressor

By Anne E. Powell, Yang Wang, Yina Li, Emily J Poulin, A. Means, M. Washington, J. Higginbotham, Alwin M. Juchheim, Nripesh Prasad, S. Levy and 6 more. Cell, 2012

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SUMMARY 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 non-cycling, long-lived stem cells located at the crypt base that, upon injury, proliferate and divide to replenish damaged crypts. Transcriptome profiling of Lrig1+ colonic stem cells differs markedly from highly proliferative, Lgr5+ colonic stem cells; genes up-regulated 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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/340ab864e9be0e9513a7ebd5e45cb406b0cc45bc

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Citations in the corpus

Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease (2018, background): “…of stem cells are present within the crypts, one that cycles actively and expresses the wnt pathway orphan receptor Lgr5, and a second, quiescent population that can replenish the Lgr5-positive pools after damage (e.g., radiation) (Barker et al. 2007; Powell et al. 2012; Wong et al. 2012).”
Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer Retrospective Analyses of the CRYSTAL and FIRE-3 Trials (2017, background): “Active signalingvia theEGFRpathway ismore frequent in patients with left-sided tumors, ostensibly rendering them more responsive to EGFR inhibitor–based therapy.(5,21) Patients with right-sided tumors have poor prognosis, which arises independent of BRAF status and does not appear to be successfully”
Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. (2014, background): “The observation, that in the APC mouse model the disruption of the pan-ErbB negative regulator LRIG1 predominantly induces distal neoplasms [24], supports the hypothesis of an important contribution of EGF signaling to distal colon carcinogenesis.”
An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control (2014, background): “A. E. Powell et al., The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.”
The intestinal crypt, a prototype stem cell compartment. (2013, background): “Lineage tracing from an Lrig1-CreERT2 allele (Powell et al., 2012) initiated at crypt bottoms along the entire length of the intestinal tract and yielded ribbons by 7 days.”