title: Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor.
abstract: TAT-RasGAP(317-326), a peptide corresponding to the 317-326 sequence of p120 RasGAP coupled with a cell-permeable TAT-derived peptide, sensitizes the death response of various tumor cells to several anticancer treatments. We now report that this peptide is also able to increase cell adherence, prevent cell migration and inhibit matrix invasion. This is accompanied by a marked modification of the actin cytoskeleton and focal adhesion redistribution. Interestingly, integrins and the small Rho GTP-binding protein, which are well-characterized proteins modulating actin fibers, adhesion and migration, do not appear to be required for the pro-adhesive properties of TAT-RasGAP(317-326). In contrast, deleted in liver cancer-1, a tumor suppressor protein, the expression of which is often deregulated in cancer cells, was found to be required for TAT-RasGAP(317-326) to promote cell adherence and inhibit migration. These results show that TAT-RasGAP(317-326), besides its ability to favor tumor cell death, hampers cell migration and invasion.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Barras
authors.affiliation: Department of Medicine, University of Fribourg, Fribourg, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Lorusso
authors.affiliation: Department of Medicine, University of Fribourg, Fribourg, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Rüegg
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Widmann
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; C430864:DLC-1 (deleted in liver cancer) protein, mouse; C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D018960:Hyaluronan Receptors; D016023:Integrins; D010446:Peptide Fragments; C525242:TAT-RasGAP(317-326); D025521:Tumor Suppressor Proteins; D054460:rho-Associated Kinases