Analysis of von Hippil-Lindau (VHL) gene in Human Renal Cancer

von Hippel-Lindau （VHL）基因的突变是家族性和散发性肾细胞癌以及许多其他器官癌症的原因。根据最近的研究，VHL蛋白（pVHL）是一种多功能肿瘤抑制蛋白，与血管生成、细胞周期退出、纤维连接蛋白基质组装和蛋白水解有关。为了研究pVHL是否影响其他重要的细胞事件，如形态发生、粘附、细胞骨架组织或运动性，我们将VHL基因引入人类肾癌和肺癌细胞，并将其与亲本细胞的影响进行比较。与未表达pvhl的细胞相比，表达pvhl的细胞形态发生了明显的变化，细胞有许多局灶性粘连和应力纤维，细胞形态呈扩张性。表达pVHL可显著提高非pVHL表达细胞的附着能力。进一步的研究表明，通过pVHL的表达，vinculin可以从细胞质转移到细胞膜上，这表明pVHL诱导了局灶性黏附的形成。与未表达pvhl的细胞相比，表达pvhl的细胞活力显著降低（P<0.05）。这些结果表明pVHL通过局灶性黏附形成稳定肌动蛋白组织，抑制细胞运动。因此，pVHL在恶性细胞的细胞骨架组织和运动中起着至关重要的作用，并作为一种独特的抑制蛋白发挥作用。

Mutation of the von Hippel-Lindau (VHL) gene is responsible for familial and sporadic renal cell carcinomas as well as for cancers in many other organs. According to recent studies, the VHL protein (pVHL) is a multifunctional tumor suppressor protein associated with the inhibition of angiogenesis, cell cycle exit, fibronectin matrix assembly, and proteolysis. To examine whether pVHL affects other important cellular events such as morphogenesis, adhision, cytoskeletal organization, or motility, we introduced the VHL gene into human kidney and lung cancer cells and compared its effects with those in parental cells. Compared with non-pVHL-expressing cells, the morphogenesis of pVHL-expressing cells was remarkably changed, with cells having many focal adhesions and stress fibers and a spreading morphology. The attachment ability of non-pVHL-expressing cells was significantly increased by expression of pVHL. Additional studies showed that vinculin was translocalized from the cytoplasm to the cell membrane by the pVHL expression, indicating induction of focal adhesion formation by pVHL. Furhtermore, motility of the pVHL-expressing cells was significantly reduced compared with that of non-pVHL-expressing cells (P<0.05). These results indicate that pVHL stabilized actin organization and inhibited cell motility through focal adhesion formation. Thus, pVHL plays a crucial rold in cytoskeletal organization and motility and functions as a unique suppressor protein in malignant cells.