Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes
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Rachel Barrow-McGee Naoki Kishi Carine Joffre Ludovic Ménard Alexia Hervieu Bakhouche A Bakhouche Alejandro J Noval Anja Mai Camilo Guzmán Luisa Robbez-Masson Xavier Iturrioz James Hulit Caroline H Brennan Ian R Hart Peter Parker Johanna Ivaska Stéphanie KermorgantAbstract
Receptor tyrosine kinases (RTKs) and integrins cooperate to stimulate cell migration and tumour metastasis. Here we report that an integrin influences signalling of an RTK, c-Met, from inside the cell, to promote anchorage-independent cell survival. Thus, c-Met and β1-integrin co-internalize and become progressively recruited on LC3B-positive 'autophagy-related endomembranes' (ARE). In cells growing in suspension, β1-integrin promotes sustained c-Met-dependent ERK1/2 phosphorylation on ARE. This signalling is dependent on ATG5 and Beclin1 but not on ATG13, suggesting ARE belong to a non-canonical autophagy pathway. This β1-integrin-dependent c-Met-sustained signalling on ARE supports anchorage-independent cell survival and growth, tumorigenesis, invasion and lung colonization in vivo. RTK-integrin cooperation has been assumed to occur at the plasma membrane requiring integrin 'inside-out' or 'outside-in' signalling. Our results report a novel mode of integrin-RTK cooperation, which we term 'inside-in signalling'. Targeting integrin signalling in addition to adhesion may have relevance for cancer therapy.
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Journal Nature Communications
Volume 7
Pages 11942
Available online
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Publisher website (DOI) 10.1038/ncomms11942
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Europe PubMed Central 27336951
Pubmed 27336951
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