Article abstract
Nature Cell Biology 2, 281 - 287 (2000)
Published online: 7 April 2000 | doi:10.1038/35010550
The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho
Richard F. Lamb1, Christian Roy2, Tom J. Diefenbach4, Harry V. Vinters3, Michael W. Johnson3, Daniel G. Jay4 & Alan Hall1
Abstract
Loss of the tumour-suppressor gene TSC1 is responsible for hamartoma development in tuberous sclerosis complex (TSC), which renders several organs susceptible to benign tumours. Hamartin, the protein encoded by TSC1, contains a coiled-coil domain and is expressed in most adult tissues, although its function is unknown. Here we show that hamartin interacts with the ezrin-radixin-moesin (ERM) family of actin-binding proteins. Inhibition of hamartin function in cells containing focal adhesions results in loss of adhesion to the cell substrate, whereas overexpression of hamartin in cells lacking focal adhesions results in activation of the small GTP-binding protein Rho, assembly of actin stress fibres and formation of focal adhesions. Interaction of endogenous hamartin with ERM-family proteins is required for activation of Rho by serum or by lysophosphatidic acid (LPA). Our data indicate that disruption of adhesion to the cell matrix through loss of hamartin may initiate the development of TSC hamartomas and that a Rho-mediated signalling pathway regulating cell adhesion may constitute a rate-limiting step in tumour formation.
- MRC Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, Gower Street, London WC1E 6BT, UK
- CNRS UMR 5539, Universite de Montpellier 2, CC107, 34095 Montpellier Cedex 05, France.
- Department of Pathology and Laboratory Medicine, Brain Research Institute, UCLA Medical Centre, Los Angeles, California 90095-1732, USA
- Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
Correspondence to: Richard F. Lamb1 e-mail: r.lamb@ucl.ac.uk
