The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3-dimensional cancer cell migration

Anjil Giri, Saumendra Bajpai, Nicholaus Trenton, Hasini Jayatilaka, Gregory D. Longmore, Denis Wirtz

Research output: Contribution to journalArticle

Abstract

Arp2/3 is a protein complex that nucleates actin filament assembly in the lamellipodium in adherent cells crawling on planar 2-dimensional (2D) substrates. However, in physiopathological situations, cell migration typically occurs within a 3-dimensional (3D) environment, and little is known about the role of Arp2/3 and associated proteins in 3D cell migration. Using time resolved live-cell imaging and HT 1080, a fibrosarcoma cell line commonly used to study cell migration, we find that the Arp2/3 complex and associated proteins N-WASP, WAVE 1, cortactin, and Cdc42 regulate 3D cell migration. We report that this regulation is caused by formation of multigeneration dendritic protrusions, which mediate traction forces on the surrounding matrix and effective cell migration. The primary protrusions emanating directly from the cell body and prolonging the nucleus forms independent of Arp2/3 and dependent on focal adhesion proteins FAK, talin, and p130Cas. The Arp2/3 complex, N-WASP, WAVE 1, cortactin, and Cdc42 regulate the secondary protrusions branching off from the primary protrusions. In 3D matrices, fibrosarcoma cells as well as migrating breast, pancreatic, and prostate cancer cells do not display lamellipodial structures. This study characterizes the unique topology of protrusions made by cells in a 3D matrix and show that these dendritic protrusions play a critical role in 3D cell motility and matrix deformation. The relative contribution of these proteins to 3D migration is significantly different from their role in 2D migration.

Original languageEnglish (US)
Pages (from-to)4089-4099
Number of pages11
JournalFASEB Journal
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • 3D environment
  • Collagen I matrix
  • Matrix deformation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3-dimensional cancer cell migration'. Together they form a unique fingerprint.

  • Cite this