Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

Rachel Barrow-McGee; Naoki Kishi; Carine Joffre; Ludovic Ménard; Alexia Hervieu; Bakhouche A Bakhouche; Alejandro J Noval; Anja Mai; Camilo Guzmán; Luisa Robert-Masson; Xavier Iturrioz; James Hulit; Caroline H Brennan; Ian R Hart; Peter J Parker; Johanna Ivaska; Stéphanie Kermorgant

doi:10.1038/ncomms11942

Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

Rachel Barrow-McGee, Naoki Kishi, Carine Joffre, Ludovic Ménard, Alexia Hervieu, Bakhouche A Bakhouche, Alejandro J Noval, Anja Mai, Camilo Guzmán, Luisa Robert-Masson, Xavier Iturrioz, James Hulit, Caroline H Brennan, Ian R Hart, Peter J Parker, Johanna Ivaska, Stéphanie Kermorgant

Comprehensive Cancer Centre

Spatial Signalling Team, Centre for Tumour Biology, Barts Cancer Institute-A Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
University of Turku, Centre for Biotechnology and VTT Technical Research Centre of Finland, FI-20520 Turku, Finland.
Francis Crick Institute
Queen Mary University of London
Centre for Tumour Biology, Barts Cancer Institute-A Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
University of Turku

Research output: Contribution to journal › Article › peer-review

90 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	11942
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11942
Publication status	Published - 23 Jun 2016

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Barrow-McGee, R., Kishi, N., Joffre, C., Ménard, L., Hervieu, A., Bakhouche, B. A., Noval, A. J., Mai, A., Guzmán, C., Robert-Masson, L., Iturrioz, X., Hulit, J., Brennan, C. H., Hart, I. R., Parker, P. J., Ivaska, J., & Kermorgant, S. (2016). Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes. Nature Communications, 7, 11942. https://doi.org/10.1038/ncomms11942

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title = "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 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. ",

author = "Rachel Barrow-McGee and Naoki Kishi and Carine Joffre and Ludovic M{\'e}nard and Alexia Hervieu and Bakhouche, {Bakhouche A} and Noval, {Alejandro J} and Anja Mai and Camilo Guzm{\'a}n and Luisa Robert-Masson and Xavier Iturrioz and James Hulit and Brennan, {Caroline H} and Hart, {Ian R} and Parker, {Peter J} and Johanna Ivaska and St{\'e}phanie Kermorgant",

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Barrow-McGee, R, Kishi, N, Joffre, C, Ménard, L, Hervieu, A, Bakhouche, BA, Noval, AJ, Mai, A, Guzmán, C, Robert-Masson, L, Iturrioz, X, Hulit, J, Brennan, CH, Hart, IR, Parker, PJ, Ivaska, J & Kermorgant, S 2016, 'Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes', Nature Communications, vol. 7, pp. 11942. https://doi.org/10.1038/ncomms11942

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T1 - Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

AU - Barrow-McGee, Rachel

AU - Kishi, Naoki

AU - Joffre, Carine

AU - Ménard, Ludovic

AU - Hervieu, Alexia

AU - Bakhouche, Bakhouche A

AU - Noval, Alejandro J

AU - Mai, Anja

AU - Guzmán, Camilo

AU - Robert-Masson, Luisa

AU - Iturrioz, Xavier

AU - Hulit, James

AU - Brennan, Caroline H

AU - Hart, Ian R

AU - Parker, Peter J

AU - Ivaska, Johanna

AU - Kermorgant, Stéphanie

PY - 2016/6/23

Y1 - 2016/6/23

N2 - 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.

AB - 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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DO - 10.1038/ncomms11942

M3 - Article

C2 - 27336951

SN - 2041-1723

VL - 7

SP - 11942

JO - Nature Communications

JF - Nature Communications

ER -

Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes

Abstract

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