Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility

Sahai, E., Olson, M. and Marshall, C. (2001) Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility. EMBO Journal, 20(4), pp. 755-766. (doi: 10.1093/emboj/20.4.755)

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Abstract

Transformation by oncogenic Ras requires the function of the Rho family GTPases. We find that Ras-transformed cells have elevated levels of RhoA-GTP, which functions to inhibit the expression of the cell cycle inhibitor p21/Waf1. These high levels of Rho-GTP are not a direct consequence of Ras signalling but are selected for in response to sustained ERR-MAP kinase signalling. While the elevated levels of Rho-GTP control the level of p21/Waf, they no longer regulate the formation of actin stress fibres in transformed cells. We show that the sustained ERK-MAP kinase signalling resulting from transformation by oncogenic Ras down-regulates ROCK1 and Rho-kinase, two Rho effecters required for actin stress fibre formation. The repression of Rho-dependent stress fibre formation by ERK-MAP kinase signalling contributes to the increased motility of Ras-transformed fibroblasts. Overexpression of the ROCK target LIM kinase restores actin stress fibres and inhibits the motility of Ras-transformed fibroblasts. We propose a model in which Ras and Rho signalling pathways cross-talk to promote signalling pathways favouring transformation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Olson, Professor Michael
Authors: Sahai, E., Olson, M., and Marshall, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:EMBO Journal
ISSN:0261-4189

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