SMAD4 and Familial prostate cancer: Overexpression of SPP1 in PCa has been confirmed by a number of studies (for detailed references please see Supplementary Table S4) followed by confirmation that SPP1, together with cyclin D1, are the key mediators of prostate cancer growth and metastatic progression within the activated TGFβ/BMP-SMAD4 signaling axis [44].