Barrow-McGee, Rachel Kishi, Naoki Joffre, Carine Ménard, Ludovic Hervieu, Alexia Bakhouche, Bakhouche A Noval, Alejandro J Mai, Anja Guzmán, Camilo Robbez-Masson, Luisa Iturrioz, Xavier Hulit, James Brennan, Caroline H Hart, Ian R Parker, Peter J Ivaska, Johanna Kermorgant, Stéphanie Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes 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. Animals;Autophagy;Carcinogenesis;Cell Adhesion;Cell Line;Cell Movement;Fibroblasts;Gene Expression Regulation;Hepatocyte Growth Factor;Humans;Integrin beta1;Mice;Proto-Oncogene Proteins c-met;Signal Transduction;Parker FC001130 2020-07-01
    https://crick.figshare.com/articles/journal_contribution/Beta_1-integrin-c-Met_cooperation_reveals_an_inside-in_survival_signalling_on_autophagy-related_endomembranes/12593837