2016
DOI: 10.1038/ncomms11942
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Beta 1-integrin–c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

Abstract: 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 … Show more

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Cited by 89 publications
(95 citation statements)
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“…Beclin1 siRNA reduced ERK1/2 activation while pERK1/2 was unchanged following ATG13 siRNA. 5 In this respect, our unpublished data also indicate that basal autophagy positively regulates phosphorylation of ERK1/2 protein in selected colorectal cancer cell lines. Further investigation is needed to unravel whether autophagy-regulated ERK1/2 phosphorylation is controlled in an RTK-dependent or independent manner.…”
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confidence: 86%
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“…Beclin1 siRNA reduced ERK1/2 activation while pERK1/2 was unchanged following ATG13 siRNA. 5 In this respect, our unpublished data also indicate that basal autophagy positively regulates phosphorylation of ERK1/2 protein in selected colorectal cancer cell lines. Further investigation is needed to unravel whether autophagy-regulated ERK1/2 phosphorylation is controlled in an RTK-dependent or independent manner.…”
mentioning
confidence: 86%
“…However, knockdown of autophagy genes did not affect c-MET phosphorylation suggesting that autophagy-related endomembranes act as scaffolds for c-MET downstream signalling cascade and ERK1/2 activation. 5 Our group has additionally found, c-MET to partially colocalise with LC3B-positive perinuclear vesicles. Unlike the study by Barrow-McGee et al, c-MET association with LC3-positive structures may affect its phosphorylation, since CQ-mediated accumulation of autophagosomes increased phosphorylation of c-MET only in autophagy-proficient conditions.…”
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confidence: 99%
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