PT  - JOURNAL ARTICLE
AU  - Sandrine Faivre
AU  - Karine Régnauld
AU  - Erik Bruyneel
AU  - Quang-Dé Nguyen
AU  - Marc Mareel
AU  - Shahin Emami
AU  - Christian Gespach
TI  - Suppression of Cellular Invasion by Activated G-Protein Subunits Gαo, Gαi1, Gαi2, and Gαi3 and Sequestration of Gβγ
AID  - 10.1124/mol.60.2.363
DP  - 2001 Aug 01
TA  - Molecular Pharmacology
PG  - 363--372
VI  - 60
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/60/2/363.short
4100  - http://molpharm.aspetjournals.org/content/60/2/363.full
SO  - Mol Pharmacol2001 Aug 01; 60
AB  - It was shown previously that platelet-activating factor receptors (PAF-Rs) inhibit invasiveness of colonic and kidney epithelial cells induced by the src and Met oncogenes via a pertussis toxin-sensitive mechanism. Therefore, Madin-Darby canine kidney (MDCKts.src) cells were stably transfected with constitutively activated forms of Gαo, Gαi1, Gαi2, Gαi3 (AGαo/i), two Gβγ sequestering proteins [C-terminal end of β-adrenergic receptor kinase (ct-βARK) and the Gαt subunit of retinal G-protein transducin], and Gβ1–Gγ2 subunits alone or in combination. Cellular invasion induced by src, Met, and leptin was abrogated by the AGαo/i, ct-βARK, and Gαt-positive clones, but was induced by coexpression of Gβ1γ2. In contrast, invasion stimulated by the trefoil factors (TFFs) pS2 and intestinal trefoil factor in MDCKts.src cells or human colonic epithelial cells PCmsrc and HCT8/S11 was insensitive to PAF, AGαo, AGαi1, and AGαi2, but was abolished by AGαi3 and the protease-activated receptor-1 (PAR-1) agonist thrombin receptor-activating peptide. Depletion of free Gβγ heterodimers by ct-βARK resulted in a remarkable decrease of cellular adhesion and spreading on collagen matrix. Our data demonstrate the following: 1) PAF-Rs impair cellular invasion induced by src, Met, and leptin via the activation of Gαo and Gαi1 to -3; 2) invasion induced by TFFs is selectively inhibited by PAR-1 receptors and Gαi3 activation; and 3) Gβγ dimers are required as positive effectors of invasion pathways induced by oncogenes and epigenetic factors. Thus, redistribution of Gαo/Gαi and Gβ/γ heterotrimeric G-proteins by PAF-R and PAR-1 exert differential functions on positive and negative signaling pathways involved in cellular invasion and may serve as potential targets for anticancer therapy.