The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho

Citation
Rf. Lamb et al., The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho, NAT CELL BI, 2(5), 2000, pp. 281-287
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
NATURE CELL BIOLOGY
ISSN journal
1465-7392 → ACNP
Volume
2
Issue
5
Year of publication
2000
Pages
281 - 287
Database
ISI
SICI code
1465-7392(200005)2:5<281:TTTSHR>2.0.ZU;2-4
Abstract
Loss of the tumour-suppressor gene TSC1 is responsible for hamartoma develo pment in tuberous sclerosis complex (TSC), which renders several organs sus ceptible 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-ra dixin-moesin (ERM) family of actin-binding proteins. Inhibition of hamartin function in cells containing focal adhesions results in loss of adhesion t o the cell substrate, whereas overexpression of hamartin in cells lacking f ocal adhesions results in activation of the small GTP-binding protein Rho, assembly of actin stress fibres and formation of focal adhesions. interacti on of endogenous hamartin with ERM-family proteins is required for activati on of Rho by serum or by lysophosphatidic acid (LPA). Our data indicate tha t disruption of adhesion to the cell matrix through loss of hamartin may in itiate the development of TSC hamartomas and that a Rho-mediated signalling pathway regulating cell adhesion may constitute a rate-limiting step in tu mour formation.