LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor

Br J Cancer. 2013 May 14;108(9):1765-70. doi: 10.1038/bjc.2013.138. Epub 2013 Apr 4.

Abstract

In baseball parlance, a triple threat is a person who can run, hit and throw with aplomb. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell surface protein that antagonises ERBB receptor signalling by downregulating receptor levels. Over 10 years ago, Hedman et al postulated that LRIG1 might be a tumour suppressor. Recently, Powell et al provided in vivo evidence substantiating that claim by demonstrating that Lrig1 loss in mice leads to spontaneously arising, highly penetrant intestinal adenomas. Interestingly, Lrig1 also marks stem cells in the gut, suggesting a potential role for Lrig1 in maintaining intestinal epithelial homeostasis. In this review, we will discuss the ability of LRIG1 to act as a triple threat: pan-ERBB negative regulator, intestinal stem cell marker and tumour suppressor. We will summarise studies of LRIG1 expression in human cancers and discuss possible related roles for LRIG2 and LRIG3.

Publication types

  • Review

MeSH terms

  • Adenoma / genetics
  • Animals
  • Biomarkers / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Genes, Tumor Suppressor
  • Humans
  • Intestinal Mucosa / metabolism
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Neoplasms / genetics*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oncogene Proteins v-erbB / antagonists & inhibitors
  • Oncogene Proteins v-erbB / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers
  • LRIG1 protein, human
  • LRIG2 protein, human
  • LRIG3 protein, human
  • Lrig1 protein, mouse
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Oncogene Proteins v-erbB
  • Tumor Suppressor Proteins
  • ErbB Receptors