Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.

Détails

Ressource 1Télécharger: BIB_08687E61E000.P001.pdf (7436.40 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_08687E61E000
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.
Périodique
Oncotarget
Auteur(s)
Lefort K., Ostano P., Mello-Grand M., Calpini V., Scatolini M., Farsetti A., Dotto G.P., Chiorino G.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
26/07/2016
Peer-reviewed
Oui
Volume
7
Numéro
30
Pages
48011-48026
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Adenocarcinomas of the prostate arise as multifocal heterogeneous lesions as the likely result of genetic and epigenetic alterations and deranged cell-cell communication. Notch signaling is an important form of intercellular communication with a role in growth/differentiation control and tumorigenesis. Contrasting reports exist in the literature on the role of this pathway in prostate cancer (PCa) development. We show here that i) compared to normal prostate tissue, Notch1 expression is significantly reduced in a substantial fraction of human PCas while it is unaffected or even increased in others; ii) acute Notch activation both inhibits and induces process networks associated with prostatic neoplasms; iii) down-modulation of Notch1 expression and activity in immortalized normal prostate epithelial cells increases their proliferation potential, while increased Notch1 activity in PCa cells suppresses growth and tumorigenicity through a Smad3-dependent mechanism involving p21WAF1/CIP1; iv) prostate cancer cells resistant to Notch growth inhibitory effects retain Notch1-induced upregulation of pro-oncogenic genes, like EPAS1 and CXCL6, also overexpressed in human PCas with high Notch1 levels. Taken together, these results reconcile conflicting data on the role of Notch1 in prostate cancer.

Mots-clé
Aged, Carcinogenesis, Cell Differentiation/physiology, Cell Line, Tumor, Cell Proliferation/physiology, Genes, Tumor Suppressor, Humans, Male, Middle Aged, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Receptor, Notch1/genetics, Receptor, Notch1/metabolism, Signal Transduction, prostate cancer, Notch
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/09/2016 15:22
Dernière modification de la notice
20/08/2019 12:30
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