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

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Title: PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation
Authors: Jo, Seung-Hee, Kim, Dong Eun, Dotto, G. Paolo, Clocchiatti, Andrea
Source: Oncotarget
Oncotarget, vol. 7, no. 37, pp. 58717-58727
Publisher Information: Impact Journals, LLC, 2016.
Publication Year: 2016
Subject Terms: 0301 basic medicine, Skin Neoplasms, Transcription, Genetic, Down-Regulation, Mice, SCID, squamous cancer, 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, Cancer-Associated Fibroblasts, RNA, Small Interfering, 0303 health sciences, RNA-Binding Proteins, 3. Good health, Keratosis, Actinic, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Carcinoma, Squamous Cell, Apoptosis Regulatory Proteins, Priority Research Paper
Description: 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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1949-2553
DOI: 10.18632/oncotarget.11227
Access URL: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=11227&path%5B%5D=35538
https://pubmed.ncbi.nlm.nih.gov/27542230
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=11227&path%5B%5D=35539
https://serval.unil.ch/resource/serval:BIB_7C3981655C04.P001/REF.pdf
https://dash.harvard.edu/handle/1/32072034
https://khepri-node.dev.meta-infra.org/papers/pdcd4-is-a-csl-associated-protein-with-a/27542230
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312270
https://serval.unil.ch/en/notice/serval:BIB_7C3981655C04
https://serval.unil.ch/resource/serval:BIB_7C3981655C04.P001/REF.pdf
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_7C3981655C044
https://serval.unil.ch/notice/serval:BIB_7C3981655C04
Rights: CC BY
Accession Number: edsair.doi.dedup.....ea12f5aaed1cf56a0d17a8e7fc46ffdd
Database: OpenAIRE
Description
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.
ISSN:19492553
DOI:10.18632/oncotarget.11227