Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes.
View/ Open
Date
2016-06-23ICR Author
Author
Barrow-McGee, R
Kishi, N
Joffre, C
Ménard, L
Hervieu, A
Bakhouche, BA
Noval, AJ
Mai, A
Guzmán, C
Robbez-Masson, L
Iturrioz, X
Hulit, J
Brennan, CH
Hart, IR
Parker, PJ
Ivaska, J
Kermorgant, S
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Cell Line
Fibroblasts
Animals
Humans
Mice
Hepatocyte Growth Factor
Cell Adhesion
Signal Transduction
Cell Movement
Gene Expression Regulation
Autophagy
Proto-Oncogene Proteins c-met
Carcinogenesis
Integrin beta1
Research team
Signal Transduction & Molecular Pharmacology
Language
eng
Date accepted
2016-05-13
License start date
2016-06-23
Citation
Nature communications, 2016, 7 pp. 11942 - ?
Publisher
NATURE PUBLISHING GROUP