VHL and renal cell carcinoma: Four HIF-1α-regulated genes (POSTN, TNFSF13B, PPEF1 and SAMSN1) were identified to be over-expressed upon VHL gene deletion in RC-VHL-KO cells in our previous study.28 These four genes could likely contribute to metastatic progression since their coordinate upregulation in patients’ tumor predicted a very poor survival in the TCGA RCC (KIRC) database.28 Amongst these four genes, we focused on POSTN because it encodes a secreted cell-adhesion protein upregulated in EMT that correlates with aggressive cancers,40,41 including RCC42 (Supplementary Fig. 4a).