Our findings suggest a critical role of pVHL172 in activating a subset of pro-tumorigenic genes, including TGFB and MMP13. Future work will be focused on characterization of the mechanistic links between pVHL172 HIF-independent functions via TGFB and/or the E3-ligase complex in cancer cell invasion and metastasis formation to consider new therapeutic strategies in the ccRCC. Here, TGFB1 is linked to cancer.