title: TGF-beta regulation of focal adhesion proteins and motility of premalignant oral lesions via protein phosphatase 1.
abstract: Premalignant oral lesions have a high incidence of recurrence and progression to malignant disease and, although studies have shown the contribution of transforming growth factor β (TGF-β) to cancer progression, none have been conducted with premalignant oral lesion cells to determine the impact of TGF-β in stimulating properties that are characteristic of more invasive cells. The present study focused on TGF-β-modulation of paxillin and the serine/threonine protein phosphatase PP-1, and the impact on cellular motility. These studies show that TGF-β stimulates premalignant lesion cell motility and up regulates expression of paxillin, as well as its co-localization with PP-1, while concurrently diminishing the level of paxillin serine phosphorylation. The TGF-β-mediated up regulation of paxillin and co-localization with actin, as well as the TGF-β-stimulated motility of premalignant lesion cells, were all blocked by inhibiting PP-1, indicating their dependence on PP-1 activity. These studies suggest interplay between TGF-β and PP-1 in promoting a more malignant phenotype in premalignant oral lesion cells.
authors.affiliation: Research Service (151), Ralph H. Johnson VA Medical Center, Charleston, SC 29401, U.S.A.
authors.forename: Jarrett E
authors.initials: JE
authors.lastname: Walsh
authors.forename: M Rita I
authors.initials: MR
authors.lastname: Young
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; D051419:Paxillin; D016212:Transforming Growth Factor beta; D054645:Protein Phosphatase 1