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Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks.

Schoenherr, C; Byron, A; Sandilands, E; Paliashvili, K; Baillie, GS; Garcia-Munoz, A; Valacca, C; ... Frame, MC; + view all (2017) Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks. Elife , 6 , Article e23172. 10.7554/eLife.23172. Green open access

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Abstract

Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described 'spatial rheostat' controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion. However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration. Spatial control of active Src requires the trafficking proteins Dynactin one and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics. We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs.

Type: Article
Title: Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.23172
Publisher version: http://dx.doi.org/10.7554/eLife.23172
Language: English
Additional information: © Schoenherr et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Ambra1, FAK, IFITM3, Src, cancer biology, cell biology, invasion, mouse, trafficking
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1550394
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