Notch signaling in the prostate: critical roles during development and in the hallmarks of prostate cancer biology
This review aims to summarize the evidence that Notch signaling is associated with prostate development, tumorigenesis and prostate tumor progression.
Studies in PubMed database were searched using the keywords of Notch signaling, prostate development and prostate cancer. Relevant literatures were identified and summarized.
The Notch pathway plays an important role in determining cell fate, proliferation, differentiation and apoptosis. Recent findings have highlighted the involvement of Notch signaling in prostate development and in the maintenance of adult prostate homeostasis. Aberrant Notch expression in tissues leads to dysregulation of Notch functions and promotes various neoplasms, including prostate cancer. High expression of Notch has been implicated in prostate cancer, and its expression increases with higher cancer grade. However, the precise role of Notch in prostate cancer has yet to be clearly defined. The roles of Notch either as an oncogene or tumor suppressor in prostate cancer hallmarks such as cell proliferation, apoptosis and anoikis, hypoxia, migration and invasion, angiogenesis as well as the correlation with metastasis are therefore discussed.
Notch signaling is a complicated signaling pathway in modulating prostate development and prostate cancer. Understanding and manipulating Notch signaling could therefore be of potential therapeutic value in combating prostate cancer.
KeywordsNotch Prostate development Prostate tumorigenesis Prostate tumor progression Prostate cancer hallmarks
This work was supported by grants from the Zhejiang Provincial Natural Science Foundation (Y2111329), Zhejiang Provincial Medicines Health Technology Project (2011KYB066), Zhejiang Provincial Traditional Medicine Technology Project (2011ZB099), Hangzhou Health Technology Project (20110833B05) and the Zhejiang Provincial Medical Association Clinical Research Funding Project (2012ZYC-A35).
Conflict of interest
The authors declare that they have no known conflicts of interest.
- Ceder JA, Jansson L, Helczynski L, Abrahamsson PA (2008) Delta-like 1 (Dlk-1), a novel marker of prostate basal and candidate epithelial stem cells, is downregulated by Notch signalling in intermediate/transit amplifying cells of the human prostate. Eur Urol 54:1344–1353. doi: 10.1016/j.eururo.2008.03.006 PubMedCrossRefGoogle Scholar
- Hayward P, Brennan K, Sanders P, Balayo T, DasGupta R, Perrimon N, Martinez Arias A (2005) Notch modulates Wnt signalling by associating with Armadillo/beta-catenin and regulating its transcriptional activity. Development 132:1819–1830. doi: 10.1242/dev.01724 PubMedCentralPubMedCrossRefGoogle Scholar
- Lavery DN, Villaronga MA, Walker MM, Patel A, Belandia B, Bevan CL (2011) Repression of androgen receptor activity by HEYL, a third member of the Hairy/Enhancer-of-split-related family of Notch effectors. J Biol Chem 286:17796–17808. doi: 10.1074/jbc.M110.198655 PubMedCentralPubMedCrossRefGoogle Scholar
- Nagel AC, Krejci A, Tenin G, Bravo-Patino A, Bray S, Maier D, Preiss A (2005) Hairless-mediated repression of Notch target genes requires the combined activity of Groucho and CtBP corepressors. Mol Cell Biol 25:10433–10441. doi: 10.1128/MCB.25.23.10433-10441.2005 PubMedCentralPubMedCrossRefGoogle Scholar
- Scorey N, Fraser SP, Patel P, Pridgeon C, Dallman MJ, Djamgoz MB (2006) Notch signalling and voltage-gated Na + channel activity in human prostate cancer cells: independent modulation of in vitro motility. Prostate Cancer Prostatic Dis 9:399–406. doi: 10.1038/sj.pcan.4500894 PubMedCrossRefGoogle Scholar
- Yu Y, Zhang Y, Guan W, Huang T, Kang J, Sheng X, Qi J (2014) Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation. Mol Cancer Res 12:830–842. doi: 10.1158/1541-7786.MCR-13-0545 PubMedCrossRefGoogle Scholar