ArticleStem cells (Dayton, Ohio)2015
p38γ MAPK Is a Therapeutic Target for Triple-Negative Breast Cancer by Stimulation of Cancer Stem-Like Cell Expansion.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Review
- Effect of a Reduced-Protein Diet Supplemented with Essential Amino Acids on the Muscle Proteome of Female and Entire Male Finishing Pigs.Animals : an open access journal from MDPI · 2025Article
- Repurposing Nilotinib as a Selective P38β Inhibitor in Hematopoietic Malignancies: Clinical Evidence and Mechanistic Insights.Journal of clinical haematology · 2025Article
- G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice.Frontiers in oncology · 2024Article
- Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.American journal of cancer research · 2024Article
- Review
- Identification of Potential p38γ Inhibitors via In Silico Screening, In Vitro Bioassay and Molecular Dynamics Simulation Studies.International journal of molecular sciences · 2023Article
- Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer.Alcohol, clinical & experimental research · 2023Article
- Pan-cancer analysis supports MAPK12 as a potential prognostic and immunotherapeutic target in multiple tumor types, including in THCA.Oncology letters · 2022Article
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- Targeting the non-ATP-binding pocket of the MAP kinase p38γ mediates a novel mechanism of cytotoxicity in cutaneous T-cell lymphoma (CTCL).FEBS letters · 2021Article
- Review
- Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells.Annals of translational medicine · 2021Article
- Regulation of cancer stem cells in triple negative breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The Role of p38γ in Cancer: From review to outlook.International journal of biological sciences · 2021Review
- Article
- Frequency of MicroRNA Response Elements Identifies Pathologically Relevant Signaling Pathways in Triple-Negative Breast Cancer.iScience · 2020Article
- Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer.Molecular & cellular proteomics : MCP · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) is highly progressive and lacks established therapeutic targets. p38γ mitogen-activated protein kinase (MAPK) (gene name: MAPK12) is overexpressed in TNBC but how overexpressed p38γ contributes to TNBC remains unknown. Here, we show that p38γ activation promotes TNBC development and progression by stimulating cancer stem-like cell (CSC) expansion and may serve as a novel therapeutic target. p38γ silencing in TNBC cells reduces mammosphere formation and decreases expression levels of CSC drivers including Nanog, Oct3/4, and Sox2. Moreover, p38γ MAPK-forced expression alone is sufficient to stimulate CSC expansion and to induce epithelial cell transformation in vitro and in vivo. Furthermore, p38γ depends on its activity to stimulate CSC expansion and breast cancer progression, indicating a therapeutic opportunity by application of its pharmacological inhibitor. Indeed, the non-toxic p38γ specific pharmacological inhibitor pirfenidone selectively inhibits TNBC growth in vitro and/or in vivo and significantly decreases the CSC population. Mechanistically, p38γ stimulates Nanog transcription through c-Jun/AP-1 via a multi-protein complex formation. These results together demonstrate that p38γ can drive TNBC development and progression and may be a novel therapeutic target for TNBC by stimulating CSC expansion. Inhibiting p38γ activity with pirfenidone may be a novel strategy for the treatment of TNBC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.