Clinical data showed increased ER-β expression in advanced-stage or high-grade tumours, correlating with unfavourable survival outcomes and reduced disease-free survival for RCC patients.68,69,115,116 ER-β has been identified as a promoter of RCC cell invasion through the augmentation of the TGF-β1/SMAD3 signalling axis. The gene discussed is SMAD3; the disease is renal cell carcinoma.