RT Journal Article SR Electronic T1 Spatial proteomics finds CD155 and Endophilin-A1 as mediators of growth and invasion in medulloblastoma JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201380 DO 10.26508/lsa.202201380 VO 5 IS 6 A1 Charles Capdeville A1 Linda Russo A1 David Penton A1 Jessica Migliavacca A1 Milica Zecevic A1 Alexandre Gries A1 Stephan CF Neuhauss A1 Michael A Grotzer A1 Martin Baumgartner YR 2022 UL https://www.life-science-alliance.org/content/5/6/e202201380.abstract AB The composition of the plasma membrane (PM)-associated proteome of tumor cells determines cell–cell and cell–matrix interactions and the response to environmental cues. Whether the PM-associated proteome impacts the phenotype of Medulloblastoma (MB) tumor cells and how it adapts in response to growth factor cues is poorly understood. Using a spatial proteomics approach, we observed that hepatocyte growth factor (HGF)-induced activation of the receptor tyrosine kinase c-MET in MB cells changes the abundance of transmembrane and membrane-associated proteins. The depletion of MAP4K4, a pro-migratory effector kinase downstream of c-MET, leads to a specific decrease of the adhesion and immunomodulatory receptor CD155 and of components of the fast-endophilin–mediated endocytosis (FEME) machinery in the PM-associated proteome of HGF-activated MB cells. The decreased surface expression of CD155 or of the fast-endophilin–mediated endocytosis effector endophilin-A1 reduces growth and invasiveness of MB tumor cells in the tissue context. These data thus describe a novel function of MAP4K4 in the control of the PM-associated proteome of tumor cells and identified two downstream effector mechanisms controlling proliferation and invasiveness of MB cells.