title: Novel insights into how autophagy regulates tumor cell motility.
abstract: Metastasis requires tumor cells to overcome a series of challenges to successfully travel to and colonize new microenvironments. As an adaptive (or maladaptive) response to stress, macroautophagy/autophagy has garnered increasing interest with respect to cancer metastasis, supported by clinical observations of increased autophagic flux in distant metastases relative to primary tumors. Recently, we identified a new role for autophagy in tumor cell motility through the turnover of focal adhesions, large multi-protein structures that link extracellular matrix-bound integrins to the cytoskeleton. The disassembly of focal adhesions at the cell rear is critical to forward movement and successful migration/invasion. We demonstrated that the focal adhesion protein PXN (paxillin), which serves as a crucial scaffolding and signal integrator, binds directly to LC3B through a conserved LC3-interacting region (LIR) motif to stimulate focal adhesion disassembly and metastasis and that this interaction is further promoted by oncogenic SRC.
authors.affiliation: a The Ben May Department for Cancer Research , University of Chicago , Chicago , IL , USA.|b Interdisciplinary Scientist Training Program , University of Chicago , Chicago , IL , USA.|c Medical Scientist Training Program , University of Chicago , Chicago , IL , USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Mowers
authors.affiliation: a The Ben May Department for Cancer Research , University of Chicago , Chicago , IL , USA.|b Interdisciplinary Scientist Training Program , University of Chicago , Chicago , IL , USA.|d The Committee on Cancer Biology , University of Chicago , Chicago , IL , USA.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Sharifi
authors.affiliation: a The Ben May Department for Cancer Research , University of Chicago , Chicago , IL , USA.|d The Committee on Cancer Biology , University of Chicago , Chicago , IL , USA.
authors.forename: Kay F
authors.initials: KF
authors.lastname: Macleod
mesh_terms: D020816:Amino Acid Motifs; D001343:Autophagy; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D051419:Paxillin
keywords: SRC; autophagy; cell motility; focal adhesion; metastasis; paxillin