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The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.
- Source :
-
Oncogene [Oncogene] 2020 Jun; Vol. 39 (23), pp. 4491-4506. Date of Electronic Publication: 2020 May 08. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
Cell Proliferation genetics
Disease Models, Animal
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic genetics
Humans
Mice
MicroRNAs genetics
Neoplasm Metastasis pathology
Protein Processing, Post-Translational genetics
Tumor Microenvironment genetics
Tumor Suppressor Protein p53 metabolism
Cell Transformation, Neoplastic genetics
Neoplasms genetics
Neoplasms pathology
Proto-Oncogene Proteins c-fos genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 39
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 32385348
- Full Text :
- https://doi.org/10.1038/s41388-020-1306-4