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

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State: Public
Version: Final published version
Serval ID
serval:BIB_08687E61E000
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer.
Journal
Oncotarget
Author(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
Publication state
Published
Issued date
26/07/2016
Peer-reviewed
Oui
Volume
7
Number
30
Pages
48011-48026
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Keywords
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
Yes
Create date
22/09/2016 15:22
Last modification date
20/08/2019 12:30
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