Research Service (151), Ralph H. Johnson VA Medical Center, Charleston, SC 29401, U.S.A.
Anticancer Res. 2011 Oct;31(10):3159-64.
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.
癌前口腔病变具有较高的复发和进展为恶性疾病的风险，尽管已有研究表明转化生长因子 β（TGF-β）对癌症进展有贡献，但尚未有研究针对癌前口腔病变细胞来确定 TGF-β在刺激更具侵袭性细胞特征的性质方面的作用。本研究集中在 TGF-β 对桩蛋白和丝氨酸/苏氨酸蛋白磷酸酶 PP-1 的调节作用，以及对细胞迁移能力的影响。这些研究表明，TGF-β 刺激癌前病变细胞的迁移，并上调桩蛋白的表达及其与 PP-1 的共定位，同时降低桩蛋白丝氨酸磷酸化水平。TGF-β 介导的桩蛋白上调及其与肌动蛋白的共定位，以及 TGF-β 刺激癌前病变细胞的迁移，均被抑制 PP-1 阻断，表明它们依赖于 PP-1 活性。这些研究表明 TGF-β 和 PP-1 之间的相互作用在促进癌前口腔病变细胞中更具恶性表型。
