F2R and melanoma: Similarly, while PAR1 induces cellular activity in tumor cells via αV integrins, in M24met melanoma cells, PAR2 has been shown to mediate migration via α5β1-dependent downstream signaling transduction molecules [272] The binding of signal proteins with a pleckstrin-homology (PH)-domain such as AKT (lipid-dependent binding), Etk/Bmx (lipid-independent binding) and Vav3 to signal-associating motifs in C-tails of PAR1 and PAR2 has been demonstrated to be critical for breast cancer progression [283].