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

Y Wang1, E J Poulin, R J Coffey

  • 1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

British Journal of Cancer
|April 6, 2013
PubMed

Insights

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) functions as a triple threat in the gut. This cell surface protein acts as a pan-ERBB negative regulator, intestinal stem cell marker, and tumor suppressor.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell surface protein known to antagonize ERBB receptor signaling.
  • Previous research suggested LRIG1 may function as a tumor suppressor.
  • Recent in vivo studies provide evidence that Lrig1 loss in mice leads to intestinal adenomas.

Purpose of the Study:

  • To review the multifaceted roles of LRIG1.
  • To discuss LRIG1 as a pan-ERBB negative regulator, intestinal stem cell marker, and tumor suppressor.
  • To summarize LRIG1 expression in human cancers and explore roles for LRIG2 and LRIG3.

Main Methods:

  • Literature review of studies on LRIG1.
  • Analysis of LRIG1's function in ERBB receptor signaling.
  • Examination of LRIG1's role in intestinal stem cells and homeostasis.

Main Results:

  • LRIG1 downregulates ERBB receptor levels, acting as a pan-ERBB negative regulator.
  • Loss of Lrig1 in mice results in spontaneous intestinal adenomas, supporting its tumor suppressor function.
  • LRIG1 marks intestinal stem cells, indicating a role in maintaining epithelial homeostasis.

Conclusions:

  • LRIG1 exhibits a "triple threat" function: negative regulation of ERBB signaling, stem cell marking, and tumor suppression.
  • Understanding LRIG1's roles is crucial for comprehending intestinal homeostasis and cancer development.
  • Further investigation into LRIG1, LRIG2, and LRIG3 in human cancers is warranted.

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