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Comment
. 2017 Feb;6(Suppl 1):S104-S108.
doi: 10.21037/tcr.2017.01.20.

Neuroendocrine differentiation in prostate cancer: key epigenetic players

Karishma Gupta  1   2 , Sanjay Gupta  1   2   3   4   5
Affiliations
Comment

Neuroendocrine differentiation in prostate cancer: key epigenetic players

Karishma Gupta et al. Transl Cancer Res. 2017 Feb.
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic model of neuroendocrine differentiation in prostate cancer. N-Myc is overexpressed after first-line or second-line androgen deprivation therapy. AURKA can bind and stabilize N-Myc in the cytosol. In the model, signaling is initiated at the membrane with receptor tyrosine kinases (RTKs) which are activated in ligand-specific manner. RTK activates PI3K through conversion by its catalytic domain of phosphatidylinositol (3,4)-bis-phosphate (PIP2) lipids to phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) where phosphatase and tensin homolog (PTEN), a tumor suppressor lipid phosphatase, converts it back to PIP2. PTEN is frequently mutated or deleted in castrate-resistant prostate cancer and its loss constitutively activates Akt, which in turn phosphorylates N-Myc. Phosphorylated N-Myc translocates to the nucleus, physically binds and forms a complex with EZH2, a catalytic subunit of PRC2 complex and abrogates AR from its binding to androgen-response elements (ARE). The interaction between N-Myc, AR, and EZH2 results in the abrogation of AR signaling, despite abundant levels of AR, represses AR targeted genes viz. prostate-specific antigen (PSA), KLK3 and NKX3.1. Notably, MYCN amplification serves an oncogenic driver in driving neuroendocrine differentiation in prostate cancer cells recognized by expression of neuroendocrine markers such as chromogranin A (CgA), SYP, and NSE. AR, androgen receptor; SYP, synaptophysin; NSE, neurospecific enolase.
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References

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