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LRIG1 (leucine-rich repeats and immunoglobulin-like domains 1)
is a transmembrane regulatory protein that negatively controls receptor tyrosine
kinases, particularly EGFR and other ERBB-family receptors. LRIG1 promotes receptor
ubiquitination, internalization and degradation, thereby reducing downstream
RAS/MAPK, PI3K/AKT and proliferative signalling. In many cancers, LRIG1 expression
is reduced or lost, which can permit persistent growth-factor signalling,
proliferation, invasion, treatment resistance and tumour progression. Restoration
or increased expression of LRIG1 has suppressed EGFR activity and cancer-cell
growth in experimental models. The typical cancer-associated direction is
down, while the desired anticancer modulation is generally
up or restoration of LRIG1 function.
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