ArticleProceedings of the National Academy of Sciences of the United States of America2013
Identification of a pharmacologically tractable Fra-1/ADORA2B axis promoting breast cancer metastasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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105 citing papers in PubMed, 183 citations in OpenAlex.
- The Role of AP-1 in Cancer: Regulation, Tumor Microenvironment and Therapeutic Targeting.Biomolecules · 2026Review
- A novel L-shaped ortho-quinone analog targeting adenosine A2b receptor to inhibit epithelial-mesenchymal transition in colorectal cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Noncoding RNAs as regulators of FOSL1 in cancer.Frontiers in immunology · 2025Review
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- Impact of the adenosine receptor A2BR expressed on myeloid cells on immune regulation during pregnancy.European journal of immunology · 2024Article
- FOSL1 is a key regulator of a super-enhancer driving TCOF1 expression in triple-negative breast cancer.Epigenetics & chromatin · 2024Article
- Current Understanding of the Role of Adenosine Receptors in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Novel role of lncRNAs regulatory network in papillary thyroid cancer.Biochemistry and biophysics reports · 2024Review
- Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.Cell reports · 2024Article
- Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner.Redox biology · 2024Article
- Adenosine receptor A2b confers ovarian cancer survival and PARP inhibitor resistance through IL-6-STAT3 signalling.Journal of cellular and molecular medicine · 2023Article
- Multiple Fra-1-bound enhancers showing different molecular and functional features can cooperate to repress gene transcription.Cell & bioscience · 2023Article
- FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023Review
- FLI1 and FRA1 transcription factors drive the transcriptional regulatory networks characterizing muscle invasive bladder cancer.Communications biology · 2023Article
- Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy.Frontiers in immunology · 2023Review
- The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy.Frontiers in immunology · 2023Review
- Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?International journal of molecular sciences · 2022Review
- P2YCancers · 2022Article
- Article
- FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis. Because Fra-1 often is overexpressed in human metastatic breast cancers and has been shown to control their invasive potential in vitro, we aimed to assess the implication and prognostic significance of the Fra-1-dependent genetic program in breast cancer metastasis and to identify potential Fra-1-dependent therapeutic targets. In several in vivo assays in mice, we demonstrate that stable RNAi depletion of Fra-1 from human breast cancer cells strongly suppresses their ability to metastasize. These results support a clinically important role for Fra-1 and the genetic program it controls. We show that a Fra-1-dependent gene-expression signature accurately predicts recurrence of breast cancer. Furthermore, a synthetic lethal drug screen revealed that antagonists of the adenosine receptor A2B (ADORA2B) are preferentially toxic to breast tumor cells expressing Fra-1. Both RNAi silencing and pharmacologic blockade of ADORA2B inhibited filopodia formation and invasive activity of breast cancer cells and correspondingly reduced tumor outgrowth in the lungs. These data show that Fra-1 activity is causally involved in and is a prognostic indicator of breast cancer metastasis. They suggest that Fra-1 activity predicts responsiveness to inhibition of pharmacologically tractable targets, such as ADORA2B, which may be used for clinical interference of metastatic breast cancer.
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