Polarised Clathrin-Mediated Endocytosis of EGFR During Chemotactic Invasion

Laura Jane Mutch, Jake Davey Howden, Emma Poppy Louise Jenner, Natalie Sarah Poulter, Joshua Zachary Rappoport*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)648-664
Number of pages17
JournalTraffic
Volume15
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Breast cancer
  • Chemotactic invasion
  • EGFR
  • Endocytosis
  • MDA-MB-231

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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