The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.
Animals
Cell Proliferation
/ genetics
Cell Transformation, Neoplastic
/ genetics
Disease Models, Animal
Epithelial-Mesenchymal Transition
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Humans
Mice
MicroRNAs
/ genetics
Neoplasm Metastasis
/ pathology
Neoplasms
/ genetics
Protein Processing, Post-Translational
/ genetics
Proto-Oncogene Proteins c-fos
/ genetics
Tumor Microenvironment
/ genetics
Tumor Suppressor Protein p53
/ metabolism
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
27
12
2019
accepted:
17
04
2020
revised:
08
04
2020
pubmed:
10
5
2020
medline:
26
11
2020
entrez:
10
5
2020
Statut:
ppublish
Résumé
Among the FOS-related members of the AP-1 dimeric complex, the transcription factor Fra-1, encoded by FOSL1, is crucially involved in human tumor progression and metastasis, thus representing a promising therapeutic target. Here we review the state of the art and discuss the emerging topics and perspectives on FOSL1 and its gene product. First, we summarize the present knowledge on the FOSL1 transcriptional and epigenetic controls, driving Fra-1 accumulation in a variety of human solid tumors. We also present a model on the regulatory interactions between Fra-1, p53, and miRNAs. Then, we outline the multiple roles of Fra-1 posttranslational modifications and transactivation mechanisms of select Fra-1 target genes. In addition to summarizing the Fra-1-dependent gene networks controlling proliferation, survival, and epithelial-mesenchymal transitions (EMT) in multiple cancer cell types, we highlight the roles played by Fra-1 in nonneoplastic cell populations recruited to the tumor microenvironment, and in mouse models of tumorigenesis. Next, we review the prognostic power of the Fra-1-associated gene signatures, and envisage potential strategies aimed at Fra-1 therapeutic inhibition. Finally, we discuss several recent reports showing the emerging roles of Fra-1 in the mechanisms of both resistance and addiction to targeted therapies.
Identifiants
pubmed: 32385348
doi: 10.1038/s41388-020-1306-4
pii: 10.1038/s41388-020-1306-4
doi:
Substances chimiques
MicroRNAs
0
Proto-Oncogene Proteins c-fos
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
fos-related antigen 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4491-4506Références
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