Heparanase mediates the expression and subcellular localization of guanine nucleotide exchange factor-H1 (GEF-H1), a component of a syndecan signaling complex, thus mediates the cross-talk between tumor cells and brain endothelia and regulates the cytoskeletal dynamics of brain metastatic melanoma and breast cancer cells [73,74]. Here, ARHGEF2 is linked to metastatic melanoma.