Knockdown of von Hippel-Lindau protein decreases lung cancer cell proliferation and colonization.

Although von Hippel-Lindau protein (pVHL) is known as a tumor suppressor in kidney and other organs, it remains unclear whether pVHL plays a role in lung cancer development. We investigated the role of pVHL in lung cancer cell proliferation, migration, and colonization using stable A549 cells with knockdown of pVHL. We found that knockdown of pVHL promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. Knockdown of pVHL decreased tumor colonization in a tail-vein injection model and decreased cell proliferation, whereas overexpression of constitutive active HIF increased tumor colonization, suggesting a HIF-independent function of pVHL in lung. Knockdown of pVHL decreased phosphorylation of FAK and expression of integrin, suggesting that pVHL regulates lung cancer development via integrin/FAK signaling pathway.