Inadequate activation of the GTPase RhoA contributes to the lack of fibronectin matrix assembly in von Hippel-Lindau protein-defective renal cancer cells

Although expression of VHL is necessary for proper extracellular matrix assembly, the mechanism by which pVHL mediates this process is not well understood. To approach this, we have evaluated the levels and functionality of the FN produced by VHL(+) and VHL(-) cells. We have also studied the role of the signaling pathway that controls formation of actin stress fibers and cell contraction in the regulation of FN matrix assembly in VHL(+) and VHL(-) cells. Our results demonstrated that FN expression levels in VHL(+) and VHL(-) cells showed no correlation with the ability to assemble a FN matrix and that VHL(-) cells expressed functional FN that was properly assembled by VHL(+) cells. Additionally, we found that the lack of FN matrix in VHL(-) cells was partly due to sustained down-regulation of RhoA activity via p190RhoGAP-increased activation. These results provide an insight into novel mechanisms altered in VHL(-) renal cancer cells.