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Cell Rep. 2016 May 24;15(8):1660-72. doi: 10.1016/j.celrep.2016.04.065. Epub 2016 May 12.

Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3.

Author information

1
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, University of Chicago, Chicago, IL 60637, USA.
2
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL 60637, USA.
3
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; Committee on Molecular Pathology, University of Chicago, Chicago, IL 60637, USA.
4
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
5
Department of Radiology, University of Chicago, Chicago, IL 60637, USA.
6
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA.
7
The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: kmacleod@uchicago.edu.

Abstract

Autophagy is a conserved catabolic process that plays a housekeeping role in eliminating protein aggregates and organelles and is activated during nutrient deprivation to generate metabolites and energy. Autophagy plays a significant role in tumorigenesis, although opposing context-dependent functions of autophagy in cancer have complicated efforts to target autophagy for therapeutic purposes. We demonstrate that autophagy inhibition reduces tumor cell migration and invasion in vitro and attenuates metastasis in vivo. Numerous abnormally large focal adhesions (FAs) accumulate in autophagy-deficient tumor cells, reflecting a role for autophagy in FA disassembly through targeted degradation of paxillin. We demonstrate that paxillin interacts with processed LC3 through a conserved LIR motif in the amino-terminal end of paxillin and that this interaction is regulated by oncogenic SRC activity. Together, these data establish a function for autophagy in FA turnover, tumor cell motility, and metastasis.

KEYWORDS:

LC3; autophagy; invasion; metastasis; paxillin

PMID:
27184837
PMCID:
PMC4880529
DOI:
10.1016/j.celrep.2016.04.065
[Indexed for MEDLINE]
Free PMC Article

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