Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis
Nature Cell BiologyPublished 4 July 2003
Erik Sahai, Christopher J. Marshall
Citations1,138
SJR quartileQ1
SJR score7.71
SNIP2.95
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TL;DR
Two modes of tumour-cell motility in 3D matrices that involve different usage of Rho signalling are identified and combined blockade of extracellular proteases and ROCK negates the ability of tumours to switch between modes of motility and synergises to prevent tumour cell invasion.
Abstract
Rho family GTPases regulate the cytoskeleton and cell migration and are frequently overexpressed in tumours. Here, we identify two modes of tumour-cell motility in 3D matrices that involve different usage of Rho signalling. Rho signalling through ROCK promotes a rounded bleb-associated mode of motility that does not require pericellular proteolysis. This form of motility requires ezrin, which is localized in the direction of cell movement. In contrast, elongated cell motility is associated with Rac-dependent F-actin-rich protrusions and does not require Rho, ROCK or ezrin function. Combined blockade of extracellular proteases and ROCK negates the ability of tumour cells to switch between modes of motility and synergises to prevent tumour cell invasion.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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