Dynamin 2 interacts with α-actinin 4 to drive tumor cell invasion

Kevin M. Burton, Hong Cao, Jing Chen, Li Qiang, Eugene W. Krueger, Katherine M. Johnson, William R. Bamlet, Lizhi Zhang, Mark A. McNiven, Gina L. Razidlo

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The large GTPase Dynamin 2 (Dyn2) is known to increase the invasiveness of pancreatic cancer tumor cells, but the mechanisms by which Dyn2 regulates changes in the actin cytoskeleton to drive cell migration are still unclear. Here we report that a direct interaction between Dyn2 and the actin-bundling protein alpha-actinin (α-actinin) 4 is critical for tumor cell migration and remodeling of the extracellular matrix in pancreatic ductal adenocarcinoma (PDAC) cells. The direct interaction is mediated through the C-terminal tails of both Dyn2 and α-actinin 4, and these proteins interact at invasive structures at the plasma membrane. While Dyn2 binds directly to both α-actinin 1 and α-actinin 4, only the interaction with α-actinin 4 is required to promote tumor cell invasion. Specific disruption of the Dyn2-αactinin 4 interaction blocks the ability of PDAC cells to migrate in either two dimensions or invade through extracellular matrix as a result of impaired invadopodia stability. Analysis of human PDAC tumor tissue additionally reveals that elevated α-actinin 4 or Dyn2 expression are predictive of poor survival. Overall, these data demonstrate that Dyn2 regulates cytoskeletal dynamics, in part, by interacting with the actin-binding protein α-actinin 4 during tumor cell invasion.

Original languageEnglish (US)
Pages (from-to)439-451
Number of pages13
JournalMolecular biology of the cell
Volume31
Issue number6
DOIs
StatePublished - Mar 15 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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