PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation.

Détails

Ressource 1Télécharger: BIB_7C3981655C04.P001.pdf (5817.49 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_7C3981655C04
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation.
Périodique
Oncotarget
Auteur(s)
Jo S.H., Kim D.E., Clocchiatti A., Dotto G.P.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Statut éditorial
Publié
Date de publication
13/09/2016
Peer-reviewed
Oui
Volume
7
Numéro
37
Pages
58717-58727
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The Notch/CSL pathway plays an important role in skin homeostasis and carcinogenesis. CSL, the key effector of canonical Notch signaling endowed with an intrinsic transcription repressive function, suppresses stromal fibroblast senescence and Cancer Associated Fibroblast (CAF) activation through direct down-modulation of key effector genes. Interacting proteins that participate with CSL in this context are as yet to be identified. We report here that Programmed Cell Death 4 (PDCD4), a nuclear/cytoplasmic shuttling protein with multiple functions, associates with CSL and plays a similar role in suppressing dermal fibroblast senescence and CAF activation. Like CSL, PDCD4 is down-regulated in stromal fibroblasts of premalignant skin actinic keratosis (AKs) lesions and squamous cell carcinoma (SCC). While devoid of intrinsic DNA binding capability, PDCD4 is present at CSL binding sites of CAF marker genes as well as canonical Notch/CSL targets and suppresses expression of these genes in a fibroblast-specific manner. Thus, we propose that PDCD4 is part of the CSL repressive complex involved in negative control of stromal fibroblasts conversion into CAFs.

Mots-clé
Animals, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, Cancer-Associated Fibroblasts/immunology, Cancer-Associated Fibroblasts/metabolism, Carcinoma, Squamous Cell/genetics, Carcinoma, Squamous Cell/metabolism, Cell Line, Tumor, Cellular Senescence, Down-Regulation, HEK293 Cells, HeLa Cells, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism, Keratosis, Actinic/genetics, Keratosis, Actinic/metabolism, Mice, Mice, SCID, Protein Binding, RNA, Small Interfering/genetics, RNA-Binding Proteins/genetics, RNA-Binding Proteins/metabolism, Signal Transduction, Skin Neoplasms/genetics, Skin Neoplasms/metabolism, Transcription, Genetic, Xenograft Model Antitumor Assays, CAFs, Notch/CSL signaling, PDCD4, squamous cancer, transcription repression
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/09/2016 17:33
Dernière modification de la notice
20/08/2019 14:37
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