title: Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3.
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.
authors.affiliation: 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.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Sharifi
authors.affiliation: 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.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Mowers
authors.affiliation: 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.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Drake
authors.affiliation: The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Collier
authors.affiliation: The Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Zamora
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mui
authors.affiliation: 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.
authors.forename: Kay F
authors.initials: KF
authors.lastname: Macleod
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D022001:Focal Adhesions / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D051419:Paxillin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D051419:Paxillin; D019061:src-Family Kinases
keywords: LC3; autophagy; invasion; metastasis; paxillin