CD155 and EndoA1 mediate growth and tissue invasion downstream of MAP4K4 in medulloblastoma cells

Abstract

How the phenotype of Medulloblastoma (MB) tumor cells adapts in response to growth factor cues is poorly understood. We systematically determined alterations in the plasma membrane (PM)-associated proteome in growth factor-activated MB cells. We found that ligand-induced activation of c-MET receptor tyrosine kinase triggers specific internalization of c-MET and of membrane-associated and transmembrane proteins including nucleoside and ion transporters. In contrast, c-MET activation caused increased PM association of the PVR/CD155 adhesion and immunomodulatory receptor, promoting MB cell motility and tumor cell growth in the cerebellar tissue. Both increased and decreased PM association of a number of these proteins including PVR/CD155 is regulated by the Ser/Thr MAP4K4. We further identified Endophilin A proteins as potential regulators of this process downstream of MAP4K4 to contribute to HGF-induced invasion control. Together, our findings describe a novel link between MAP4K4 overexpression in MB and the maintenance of a cellular phenotype associated with growth and invasiveness.