期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11942
关键词
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资金
- UK Medical Research Council (MRC)
- MRC Centenary Award
- Barts and The London Charity [472/1711]
- Rosetrees Trust [M314, M346]
- MRC [MR/J500409/1, G0501003]
- Barts and The London Charitable Foundation Scholarship [RAB 05/PJ/07]
- CR-UK [C236/A11795]
- Breast Cancer Now [2008NovPR10]
- Academy of Finland
- ERC
- Finnish Cancer Organisations and Sigrid Juselius Foundation
- British Lung Foundation [CAN09-4]
- MRC [G0501003] Funding Source: UKRI
- British Lung Foundation [CAN09-4] Funding Source: researchfish
- Cancer Research UK [15683] Funding Source: researchfish
- Medical Research Council [G0501003, 1094678] Funding Source: researchfish
- Pancreatic Cancer UK [FLF2015_02_Barts] Funding Source: researchfish
- Rosetrees Trust [M314-F1] Funding Source: researchfish
- The Francis Crick Institute [10130] Funding Source: researchfish
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 beta 1-integrin co-internalize and become progressively recruited on LC3B-positive 'autophagy-related endomembranes' (ARE). In cells growing in suspension, beta 1-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 beta 1-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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