title: Harnessing membrane trafficking to promote cancer spreading and invasion: The case of RAB2A.
abstract: How cancer disseminates and metastasizes remains an outstanding open question. Emerging evidence indicates that membrane trafficking is frequently harnessed by tumors of epithelial origin to acquire a mesenchymal program of invasiveness. However, the critical molecular hubs used by cancer cells this context have only began to be elucidated. Here, we discussed the results of a recent phenotypic screening that led to the identification of the small GTPase RAB2A, not previously involved in cancer dissemination, as pivotal for the acquisition of pericellular proteolysis, cell dissemination and distant metastatic spreading of human breast cancer. At the cellular levels, RAB2A controls both canonical polarized Golgi-to-Plasma membrane trafficking of the junctional protein E-cadherin, and post-endocytic trafficking of the membrane-bound metalloprotease, MT1-MMP. This finding reveals an unexpected plasticity in the control of diverse trafficking routes exerted by RAB2A through canonical (Golgi stacking) and non-canonical (late endosome recycling) functional interactions, contributing to break established membrane trafficking dogma on the rigorous molecular distinction between polarized Golgi and post endocytic routes. Finally, they suggest that epithelial cancers may specifically select for those molecules that enable them to control multiple trafficking routes, in turn essential for the regulation of activities necessary for acquisition of mesenchymal traits.
authors.affiliation: a IFOM, the FIRC Institute of Molecular Oncology , Milan , Italy.|b Division of Membrane Dynamics, Department of Physiology and Cell Biology , Kobe University Graduate School of Medicine Kobe City , Hyogo , Japan.
authors.forename: Hiroaki
authors.identifier: 0000-0001-6376-7629
authors.initials: H
authors.lastname: Kajiho
authors.affiliation: a IFOM, the FIRC Institute of Molecular Oncology , Milan , Italy.|c Department of Pediatrics , Graduate School of Medicine, The University of Tokyo , Bunkyo-ku, Tokyo , Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kajiho
authors.affiliation: a IFOM, the FIRC Institute of Molecular Oncology , Milan , Italy.|d Department of Oncology and Hemato-Oncology , DIPO, Università degli Studi di Milano , Milan , Italy.
authors.forename: Giorgio
authors.identifier: 0000-0001-7984-1889
authors.initials: G
authors.lastname: Scita
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; D020691:rab GTP-Binding Proteins
keywords: E-cadherin; MT1-MMP; RAB GTPases; RAB2A; cancer migration and invasion; membrane trafficking