TFRC and nonpapillary renal cell carcinoma: Interestingly, the VHL gene is mutated or hypermethylated in about 90% of all ccRCC patients, with its loss of function leading to the accumulation of HIF-α.1 In turn, HIF-α is essential to regulate the expression of a variety of iron-regulated genes, including TfR, ferritin and ferroportin.40 Thus, the HIF-α signalling pathway might be essential to control cellular iron trafficking and mobilisation, which is important to promote tumour growth.