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von Hippel-Lindau Protein Promotes the Assembly of Actin and Vinculin and Inhibits Cell Motility¹

Department of Urology, Kochi Medical School, Nankoku, 783-8505, Japan [M. K., H. O., T. S.]; Laboratory of Radiation and Life Science, School of Pharmaceutical Sciences, Nagasaki University, Nagasaki 852-8521, Japan [K. S.]; Kanagawa Dental College, Department of Biochemistry, Yokosuka, 238-8580, Japan [Y. K.]

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, adhesion, 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. Furthermore, 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 role in cytoskeletal organization and motility and functions as a unique suppressor protein in malignant cells.

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