title: Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.
abstract: Directed cell migration is critical for numerous physiological processes including development and wound healing. However chemotaxis is also exploited during cancer progression. Recent reports have suggested links between vesicle trafficking pathways and directed cell migration. Very little is known about the potential roles of endocytosis pathways during metastasis. Therefore we performed a series of studies employing a previously characterised model for chemotactic invasion of cancer cells to assess specific hypotheses potentially linking endocytosis to directed cell migration. Our results demonstrate that clathrin-mediated endocytosis is indispensable for epidermal growth factor (EGF) directed chemotactic invasion of MDA-MB-231 cells. Conversely, caveolar endocytosis is not required in this mode of migration. We further found that chemoattractant receptor (EGFR) trafficking occurs by clathrin-mediated endocytosis and is polarised towards the front of migrating cells. However, we found no role for clathrin-mediated endocytosis in focal adhesion disassembly in this migration model. Thus, this study has characterised the role of endocytosis during chemotactic invasion and has identified functions mechanistically linking clathrin-mediated endocytosis to directed cell motility.
authors.forename: Laura Jane
authors.initials: LJ
authors.lastname: Mutch
authors.forename: Jake Davey
authors.initials: JD
authors.lastname: Howden
authors.forename: Emma Poppy Louise
authors.initials: EP
authors.lastname: Jenner
authors.forename: Natalie Sarah
authors.initials: NS
authors.lastname: Poulter
authors.forename: Joshua Zachary
authors.initials: JZ
authors.lastname: Rappoport
mesh_terms: D045744:Cell Line, Tumor; D002633:Chemotaxis; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans
chemical_list: D066246:ErbB Receptors