PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation
| Autor: | Seung-Hee Jo, Andrea Clocchiatti, G. Paolo Dotto, Dong-Eun Kim |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Skin Neoplasms Stromal cell Transcription Genetic Notch signaling pathway Down-Regulation Mice SCID Biology medicine.disease_cause squamous cancer Dermal fibroblast Mice 03 medical and health sciences 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 HEK293 Cells HeLa Cells Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism Keratosis Actinic/genetics Keratosis Actinic/metabolism Protein Binding RNA Small Interfering/genetics RNA-Binding Proteins/genetics RNA-Binding Proteins/metabolism Signal Transduction Skin Neoplasms/genetics Skin Neoplasms/metabolism Xenograft Model Antitumor Assays CAFs Notch/CSL signaling PDCD4 transcription repression 0302 clinical medicine Cancer-Associated Fibroblasts Transcription (biology) medicine RNA Small Interfering Fibroblast Effector RNA-Binding Proteins 3. Good health Keratosis Actinic 030104 developmental biology medicine.anatomical_structure Oncology Immunoglobulin J Recombination Signal Sequence-Binding Protein 030220 oncology & carcinogenesis Immunology Carcinoma Squamous Cell Cancer research Signal transduction Apoptosis Regulatory Proteins Carcinogenesis Priority Research Paper |
| Zdroj: | Oncotarget, vol. 7, no. 37, pp. 58717-58727 Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11227 |
| Popis: | // Seung-Hee Jo 1,2 , Dong Eun Kim 3 , Andrea Clocchiatti 1,2 and G. Paolo Dotto 1,3 1 Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA 2 Department of Dermatology, Harvard Medical School, Boston, MA, USA 3 Department of Biochemistry, University of Lausanne, Epalinges, CH, Switzerland Correspondence to: G. Paolo Dotto, email: // Keywords : PDCD4, Notch/CSL signaling, transcription repression, squamous cancer, CAFs Received : May 12, 2016 Accepted : July 22, 2016 Published : August 11, 2016 Abstract 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. |
| Databáze: | OpenAIRE |
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