The TSC1 Tumour Suppressor Hamartin Regulates Cell Adhesion Through ERM Proteins and The GTPase Rho.

Publication/Presentation Date

5-1-2000

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.

Volume

2

Issue

5

First Page

281

Last Page

287

ISSN

1465-7392

Disciplines

Medical Pathology | Pathology

PubMedID

10806479

Peer Reviewed for front end display

Peer-Reviewed

Department(s)

Department of Pathology and Laboratory Medicine, Pathology Laboratory Medicine Faculty

Document Type

Article

Link to Full Text

Share

COinS