LGRs receptors as peculiar GPCRs involved in cancer

G protein-coupled receptors (GPCRs) constitute the largest protein superfamily in mammalian genomes. The Leucine-rich repeat-containing G protein-coupled receptors LGR4, LGR5 and LGR6 belong to the type A rhodopsin-like family and are closely structurally related to the glycoprotein hormone receptors. They have the particularity to be expressed in stem/progenitor cells. LGRs commonly recognize R-spondins as ligands leading to Wnt signaling regulation. Whereas LGR4 plays an essential role during development and adult homeostasis and exerts a dominant function over its paralogues, the function of LGR5 still remains controversial. In cancer cells, LGRs identify tumor-initiating cells and their expression can be correlated with tumor stage and prognosis. The molecular events underlying deregulated expression of LGRs in cancer cells and potential new therapeutic approaches to target cancer cells are reviewed.