ROCK- and Myosin-Dependent Matrix Deformation Enables Protease-Independent Tumor-Cell Invasion In Vivo

Jeffrey B. Wyckoff, Sophie E. Pinner, Steve Gschmeissner, John S. Condeelis, Erik Sahai

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

Tumor cells invading three-dimensional matrices need to remodel the extracellular matrix (ECM) in their path. Many studies have focused on the role of extracellular proteases [1, 2]; however, cells with amoeboid or rounded morphologies are able to invade even when these enzymes are inhibited [3, 4]. Here, we describe the mechanism by which cells move through a dense ECM without proteolysis. Amoeboid tumor cells generate sufficient actomyosin force to deform collagen fibers and are able to push through the ECM. Force generation is elevated in metastatic MTLn3E cells, and this correlates with increased invasion and altered myosin light chain (MLC) organization. In metastatic cells, MLC is organized perpendicularly to the direction of movement behind the invading edge. Both the organization of MLC and force generation are dependent upon ROCK function. We demonstrate that ROCK regulates the phosphorylation of MLC just behind the invading margin of the cell. Imaging of live tumors shows that MLC is organized in a similar ROCK-dependent fashion in vivo and that inhibition of ROCK but not matrix-metalloproteases reduces cancer cell motility in vivo.

Original languageEnglish (US)
Pages (from-to)1515-1523
Number of pages9
JournalCurrent Biology
Volume16
Issue number15
DOIs
StatePublished - Aug 8 2006

Fingerprint

myosin light chains
Myosin Light Chains
cell invasion
Myosins
myosin
Tumors
Peptide Hydrolases
proteinases
extracellular matrix
Cells
Neoplasms
Extracellular Matrix
cells
Proteolysis
Actomyosin
Phosphorylation
Metalloproteases
metalloproteinases
cell movement
proteolysis

Keywords

  • CELLBIO
  • CELLCYCLE
  • SIGNALING

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

ROCK- and Myosin-Dependent Matrix Deformation Enables Protease-Independent Tumor-Cell Invasion In Vivo. / Wyckoff, Jeffrey B.; Pinner, Sophie E.; Gschmeissner, Steve; Condeelis, John S.; Sahai, Erik.

In: Current Biology, Vol. 16, No. 15, 08.08.2006, p. 1515-1523.

Research output: Contribution to journalArticle

Wyckoff, Jeffrey B. ; Pinner, Sophie E. ; Gschmeissner, Steve ; Condeelis, John S. ; Sahai, Erik. / ROCK- and Myosin-Dependent Matrix Deformation Enables Protease-Independent Tumor-Cell Invasion In Vivo. In: Current Biology. 2006 ; Vol. 16, No. 15. pp. 1515-1523.
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