The neural guidance receptor Plexin C1 delays melanoma progression.

摘要: Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, express high levels C1, lost melanoma vitro vivo. To determine if tumor suppressor we introduced into primary cell line, phenotypes including migration, apoptosis, proliferation growth mice were analyzed. Complimentary studies was silenced melanocytes performed. significantly inhibited migration whereas melanocytes, loss increased proliferation. In mouse xenografts, delayed at early time points, but tumors eventually escaped suppressive effects due to C1-dependent activation pro-survival protein Akt. stimulates migration. lowered activity consistent inhibitory on melanoma. expressed melanocytic lesions vivo, staining tissue microarrays nevi expression highly limited lesions, being essentially confined almost completely absent metastatic These data suggest that may promote steps progression through suppression proliferation, ultimately abrogate C1. function by releasing inhibition activation, stimulating