Back to Search
Start Over
FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2023 May 05; Vol. 24 (9). Date of Electronic Publication: 2023 May 05. - Publication Year :
- 2023
-
Abstract
- Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by FOSL1 ) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which FOSL1 is overexpressed in the TNBC (Triple Negative Breast Cancer)/basal subtypes, correlates with the FRA-1-dependent transcriptional regulation of EMT (Epithelial-to-Mesenchymal Transition). After summarizing the major findings on FRA-1 in breast cancer invasiveness, we discuss the FRA-1 mechanistic links with EMT and cancer cell stemness, mediated by transcriptional and posttranscriptional interactions between FOSL1 /FRA-1 and EMT-regulating transcription factors, miRNAs, RNA binding proteins and cytokines, along with other target genes involved in EMT. In addition to the FRA-1/AP-1 effects on the architecture of target promoters, we discuss the diagnostic and prognostic significance of the EMT-related FRA-1 transcriptome, along with therapeutic implications. Finally, we consider several novel perspectives regarding the less explored roles of FRA-1 in the tumor microenvironment and in control of the recently characterized hybrid EMT correlated with cancer cell plasticity, stemness, and metastatic potential. We will also examine the application of emerging technologies, such as single-cell analyses, along with animal models of TNBC and tumor-derived CTCs and PDXs (Circulating Tumor Cells and Patient-Derived Xenografts) for studying the FRA-1-mediated mechanisms in in vivo systems of EMT and metastasis.
- Subjects :
- Animals
Humans
Cell Line, Tumor
Cell Movement
Disease Models, Animal
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic
Neoplasm Metastasis
Transcription Factor AP-1 metabolism
Tumor Microenvironment
MicroRNAs genetics
Triple Negative Breast Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 37176013
- Full Text :
- https://doi.org/10.3390/ijms24098307