Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens.

Abstract:

:Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these pathways are redundant; blockade of any one pathway can be overcome by stimulation of another. This implies that a more effective approach would be to target a component at which these pathways converge. In this study, we have investigated whether the molecular motor myosin II represents such a target by examining glioma invasion in a series of increasingly complex models that are sensitive to platelet-derived growth factor, epidermal growth factor, or both. Our results lead to two conclusions. First, malignant glioma cells are stimulated to invade brain through the activation of multiple signaling cascades not accounted for in simple in vitro assays. Second, even though there is a high degree of redundancy in promigratory signaling cascades in gliomas, blocking tumor invasion by directly targeting myosin II remains effective. Our results thus support our hypothesis that myosin II represents a point of convergence for signal transduction pathways that drive glioma invasion and that its inhibition cannot be overcome by other motility mechanisms.

journal_name

Mol Biol Cell

authors

Ivkovic S,Beadle C,Noticewala S,Massey SC,Swanson KR,Toro LN,Bresnick AR,Canoll P,Rosenfeld SS

doi

10.1091/mbc.E11-01-0039

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

533-42

issue

4

eissn

1059-1524

issn

1939-4586

pii

mbc.E11-01-0039

journal_volume

23

pub_type

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