Understanding c-Met endosomal signalling in cancer
| Dates: | 31 October 2017 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Stéphanie Kermorgant |
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RTKs contribute to many facets of cell behaviour which play integral roles in tumour development and progression. It is increasingly recognized that RTKs continue their signalling life cycle post-endocytosis, while trafficking through endosomal compartments. The RTK c-Met, (hepatocyte growth factor (HGF) receptor), is overexpressed in many cancers including breast (20-30%) and pancreatic (60-80%) cancers, with levels of expression correlating with poor prognosis. Importantly, c-Met contributes to resistance to existing therapies such as gemcitabine in pancreatic cancer. We demonstrated that the signalling on endosomes of c-Met plays a central role in cell migration, growth and malignant transformation (Kermorgant and Parker, J Cell Biol 2008, Joffre et al., Nat Cell Biol, 2011, Menard et al., Nat Commun, 2014). More surprisingly, we discovered that, in several cell systems, c-Met and beta1-integrin co-internalise and accumulate on endomembranes positive for LC3B (Microtubule-associated protein 1A/1B-light chain 3) and Beclin1, autophagy markers. Our current model is that from these autophagic molecules, c-Met sustains signalling leading to increase survival in anoikis (Barrow-McGee et al. Nat Commun, 2016). Currently, we are analyzing c-Met endosomal signalling in breast and pancreatic cancer. Our work may lead to the development of strategies to reduce the signalling of c-Met in cancer.
Speaker
Stéphanie Kermorgant
Organisation: Barts Cancer Institute
Travel and Contact Information
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Michael Smith Lecture Theatre
Michael Smith Building
Manchester
