GPRC5A exerts its tumor-suppressive effects in breast cancer cells by inhibiting EGFR and its downstream pathway.

G-protein-coupled receptor family C group 5 member A (GPRC5A) is a member of the type 3-G protein‑coupling receptor family. Previous studies have observed dysregulated expression of GPRC5A in several malignant diseases which suggests that GPRC5A may participate in tumor progression. However, these results are controversial. In the present study, we explored the biological functions of GPRC5A in breast cancer cells and aimed to uncover the related molecular mechanisms. Our results demonstrated that GPRC5A is a tumor suppressor in EGFR-expressing breast cancer cells. GPRC5A knockdown in EGFR-expressing MDA-MB-231 cells promoted colony formation, cell proliferation, cell migration and invasion, while GPRC5A suppression had no impact on MCF7 cells, which express no EGFR. Furthermore, GPRC5A knockdown enhanced EGF-induced EGFR and its downstream signaling activation. Inhibition of EGFR phosphorylation in MDA-MB-231 cells suppressed the tumorigenic effects of GPRC5A knockdown. Moreover, GPRC5A knockdown exhibited an oncogenic role in MCF7 cells transfected with the EGFR-expressing plasmid. Taken together, our results implicate GPRC5A as a tumor suppressor in breast cancer cells, and GPRC5A exerts its tumor-suppressive function by inhibiting EGFR and its downstream pathway.