This review focuses on the role of Notch-1 in prostate cancer development and maintenance and relates this to the fundamental role of Notch in normal prostate development.
Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation.
By comparing candidate driving genes between AYA cancers and those from all age groups for the same type of cancer, we identified different driving genes in prostate cancer and a germ cell tumor in AYAs compared with all age groups, whereas three common alterations (TP53, FAT1, and NOTCH1) in head and neck cancer were identified in both groups.
In PCa and lymph node metastasis, expression of SOX2 and NOTCH1 was highly related to that of SNAI2.In conclusion, I. SNAI2 silencing in PCa may turn-off the expression of NED markers and pluripotency genes, while turning-on that of specific metastasis-suppressors, II.
These results suggest that down-regulation of Notch-1 by novel agents could become a newer approach for the prevention of tumor progression and/or treatment, which is likely to be mediated via inactivation of Akt and FoxM1 signaling pathways in PCa.
In situ hybridization and reverse transcription-PCR analyses revealed that Notch1 was expressed in prostate epithelial cells during normal development and in prostate cancer cells.