ArticleNature medicine2017
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 102 citations in OpenAlex.
- DUSP1 is a key driver of disease persistence and potential therapeutic target in hairy cell leukemia.Blood advances · 2026Article
- Early radiotherapy delays acquired gefitinib resistance in EGFR-mutant NSCLC by suppressing c-FOS-associated survival signaling.Respiratory research · 2026Article
- MEK Inhibitors and Toll-like Receptor Signaling: Implications for Infection and Inflammation.International journal of molecular sciences · 2026Review
- Single nuclei RNA-sequencing unveils alveolar macrophages as drivers of endothelial damage in obese HFpEF-related pulmonary hypertension.Cardiovascular diabetology · 2025Article
- NR4A1 suppresses breast cancer growth by repressing c-Fos-mediated lipid and redox dyshomeostasis.Experimental & molecular medicine · 2025Article
- Acetylation-regulated DUSP1 deficiency contributes to renal fibrosis progression.Theranostics · 2025Article
- N6-methyladenosine methylation analysis of long noncoding RNAs and mRNAs in 5-FU-resistant colon cancer cells.Epigenetics · 2024Article
- A High-Throughput Screen for Antiproliferative Peptides in Mammalian Cells Identifies Key Transcription Factor Families.ACS synthetic biology · 2024Article
- Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression.Redox biology · 2024Article
- Article
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- Enhanced MAPK signaling induced by CSF3R mutants confers dependence to DUSP1 for leukemic transformation.Blood advances · 2024Article
- Surgical Tumor Resection Deregulates Hallmarks of Cancer in Resected Tissue and the Surrounding Microenvironment.Molecular cancer research : MCR · 2024Article
- TIF1β activates leukemic transcriptional program in HSCs and promotes BCR::ABL1-induced myeloid leukemia.Leukemia · 2024Article
- CD38 promotes hematopoietic stem cell dormancy.PLoS biology · 2024Article
- Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease.Nature communications · 2024Article
- c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer.Cell death & disease · 2024Article
- Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.RNA biology · 2024Review
- Regulation of ferroptosis-related genes in CD8+ NKT cells and classical monocytes may affect the immunotherapy response after combined treatment in triple negative breast cancer.Thoracic cancer · 2023Article
- EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.Journal of biomolecular structure & dynamics · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1). Genetic deletion of Fos and Dusp1 suppressed tumor growth in a BCR-ABL fusion protein kinase-induced mouse model of chronic myeloid leukemia (CML). Pharmacological inhibition of c-FOS, DUSP1 and BCR-ABL eradicated MRD in multiple in vivo models, as well as in mice xenotransplanted with patient-derived primary CML cells. Growth-factor signaling also conferred TKI resistance and induced FOS and DUSP1 expression in tumor cells modeling other types of kinase-driven leukemias. Our data demonstrate that c-FOS and DUSP1 expression levels determine the threshold of TKI efficacy, such that growth-factor-induced expression of c-FOS and DUSP1 confers intrinsic resistance to TKI therapy in a wide-ranging set of leukemias, and might represent a unifying Achilles' heel of kinase-driven cancers.
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