Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

External organisations

  • School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: t.d.williams@bham.ac.uk.

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.

Details

Original languageEnglish
Pages (from-to)648-664
JournalTraffic
Volume15
Issue number6
Early online date20 Mar 2014
Publication statusPublished - 1 Jun 2014

Keywords

  • breast cancer, chemotactic invasion, EGFR, endocytosis, MDA-MB-231