%0 Journal Article %A Barrow-McGee, Rachel %A Kishi, Naoki %A Joffre, Carine %A Ménard, Ludovic %A Hervieu, Alexia %A Bakhouche, Bakhouche A %A Noval, Alejandro J %A Mai, Anja %A Guzmán, Camilo %A Robbez-Masson, Luisa %A Iturrioz, Xavier %A Hulit, James %A Brennan, Caroline H %A Hart, Ian R %A Parker, Peter J %A Ivaska, Johanna %A Kermorgant, Stéphanie %D 2020 %T Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes %U https://crick.figshare.com/articles/journal_contribution/Beta_1-integrin-c-Met_cooperation_reveals_an_inside-in_survival_signalling_on_autophagy-related_endomembranes/12593837 %2 https://crick.figshare.com/ndownloader/files/23581217 %K Animals %K Autophagy %K Carcinogenesis %K Cell Adhesion %K Cell Line %K Cell Movement %K Fibroblasts %K Gene Expression Regulation %K Hepatocyte Growth Factor %K Humans %K Integrin beta1 %K Mice %K Proto-Oncogene Proteins c-met %K Signal Transduction %K Parker FC001130 %X 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. %I The Francis Crick Institute