FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer
Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by <i>FOSL1</i>) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which <i>FOSL1</i> is overexpressed in t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8307 |
| _version_ | 1797602356811005952 |
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| author | Laura Casalino Francesco Talotta Ilenia Matino Pasquale Verde |
| author_facet | Laura Casalino Francesco Talotta Ilenia Matino Pasquale Verde |
| author_sort | Laura Casalino |
| collection | DOAJ |
| description | Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by <i>FOSL1</i>) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which <i>FOSL1</i> 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 <i>FOSL1</i>/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. |
| first_indexed | 2024-03-11T04:15:54Z |
| format | Article |
| id | doaj.art-252301541f244a6da62e77333d59944c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:15:54Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-252301541f244a6da62e77333d59944c2023-11-17T23:07:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249830710.3390/ijms24098307FRA-1 as a Regulator of EMT and Metastasis in Breast CancerLaura Casalino0Francesco Talotta1Ilenia Matino2Pasquale Verde3Institute of Genetics and Biophysics “A. Buzzati Traverso”, Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino, 111, 80131 Naples, ItalyInstitute of Genetics and Biophysics “A. Buzzati Traverso”, Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino, 111, 80131 Naples, ItalyInstitute of Genetics and Biophysics “A. Buzzati Traverso”, Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino, 111, 80131 Naples, ItalyInstitute of Genetics and Biophysics “A. Buzzati Traverso”, Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino, 111, 80131 Naples, ItalyAmong FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by <i>FOSL1</i>) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which <i>FOSL1</i> 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 <i>FOSL1</i>/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.https://www.mdpi.com/1422-0067/24/9/8307AP-1 transcription factorsFRA-1<i>FOSL1</i>TNBCEMT |
| spellingShingle | Laura Casalino Francesco Talotta Ilenia Matino Pasquale Verde FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer International Journal of Molecular Sciences AP-1 transcription factors FRA-1 <i>FOSL1</i> TNBC EMT |
| title | FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer |
| title_full | FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer |
| title_fullStr | FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer |
| title_full_unstemmed | FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer |
| title_short | FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer |
| title_sort | fra 1 as a regulator of emt and metastasis in breast cancer |
| topic | AP-1 transcription factors FRA-1 <i>FOSL1</i> TNBC EMT |
| url | https://www.mdpi.com/1422-0067/24/9/8307 |
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