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. 2014 Apr 9;6(2):829-59.
doi: 10.3390/cancers6020829.

"VSports在线直播" The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer

Jennifer L Bishop  1 , Daksh Thaper  2 , Amina Zoubeidi  3
Affiliations

The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer (V体育平台登录)

Jennifer L Bishop et al. Cancers (Basel). .

Abstract

The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer VSports手机版. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent prostate cancer progression and the variety of STAT3 inhibitors used in cancer therapies is discussed. .

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Figures

Figure 1
Figure 1
STAT3 integrates different signaling pathways involved in prostate cancer progression to metastatic disease. Binding of ligands to Cytokine Receptors and or Receptor Tyrosine Kinases recruits non-receptor Tyrosine kinases (JAK family and Src family) through their SH2 domains to the receptors. The same SH2 interaction also recruits STAT3 to the receptors and STAT3 gets phosphorylated on Tyrosine 705 by the non-receptor kinases leading to its dimerization, nuclear translocation and binding to DNA of target genes involved proliferation (CyclinD1, cMyc, Mcl1), Angiogenesis (Hif1α and VEGF), EMT (Twist, MMP2, 9, 7). In addition to this, the activity of mTOR and MAPK pathways phosphorylates STAT3 at Serine 727 which directly interacts with the NTD of the Androgen Receptor promoting its differentiation activity without increasing cell proliferation.
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