As a transcription factor, E2F3 directly targets IL-6 signaling and is involved in prostate tumorigenesis (Libertini et al., 2012), and dysregulation of the E2F5/p38/SMAD3 circuitry has been found to reinforce the protumorigenic switch of TGFβ signaling in prostate cancer (Majumder et al., 2016). Here, E2F5 is linked to Familial prostate cancer.