When ectopically overexpressed in murine B16F10 melanoma cells, activation of GPR4 by acidosis has several effects on tumor cell function such as decreasing cell membrane protrusions, inhibiting cancer cell migration, and reducing melanoma cell lung metastasis through the G12/13/Rho pathway; whereas GPR4 does not significantly inhibit primary B16F10 melanoma growth (Castellone et al., 2011; Zhang et al., 2012). This evidence concerns the gene RHO and melanoma.