Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer

Figure 4

The JAK/STAT signaling in prostate cancer. (1) The JAK/STAT pathway has been found constitutively activated in PCa cells, leading to induction of tumor cell proliferation and apoptosis inhibition mediated by STAT3 activation. (2) BRCA1/2 is required for DNA repair in normal cells. However, in PCa, BRCA1 can bind STAT3 to promote JAK/STAT3 activation. (3) AR is a well-characterized cross-talk pathway in PCa. When activated, AR can bind to STAT3 leading to the activation of JAK/STAT cascade, being important in the induction of cell proliferation and apoptosis inhibition. (4) Under stress conditions, ATF3 is activated and plays a crucial role in the maintenance of cell integrity and homeostasis. ATF3 does so by interacting with AR, leading to inhibition of androgen signaling and, consequently, the inhibition of cell proliferation. However, ATF3 is downregulated in PCa cells, suggesting that this pathway provides an important mechanism of defense against cancer. (5) Similarly, C/EBPδ is required to inhibit cell proliferation by binding to STAT3. Nevertheless, C/EBPδ is typically downregulated in PCa, and, therefore, it could be used as an strategy in the development of therapeutic drugs against PCa growth.