Polarised Clathrin‐Mediated Endocytosis of EGFR During Chemotactic Invasion |
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Authors: | Laura Jane Mutch Jake Davey Howden Emma Poppy Louise Jenner Natalie Sarah Poulter Joshua Zachary Rappoport |
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Affiliation: | 1. School of Biosciences, The University of Birmingham, , Edgbaston, Birmingham, B15 2TT UK;2. Centre for Cardiovascular Research, Institute for Biomedical Research, The College of Medical and Dental Sciences, The University of Birmingham, , Edgbaston, Birmingham, B15 2TT UK |
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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. |
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Keywords: | breast cancer chemotactic invasion EGFR endocytosis MDA‐MB‐231 |
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