ArticleCancer research2014
Mitochondrial MKP1 is a target for therapy-resistant HER2-positive breast cancer cells.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
The trial behind it
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
27 citing papers in PubMed, 77 citations in OpenAlex.
- Effect of siRNA-mediated knockdown of the PD-L1 (CD274) gene on DUSP gene family expression and potential clinical implications in gastric cancer.Medical oncology (Northwood, London, England) · 2026Article
- DUSP1: Triple-Negative Breast Cancer and Therapeutic Potential.Current oncology (Toronto, Ont.) · 2026Review
- Review
- Bioinformatic analysis, clinical implications and experimental validation of ferroptosis-related feature gene in IgA nephropathy: focus on DUSP1.Frontiers in medicine · 2025Article
- Aldo-keto reductase family 1 member C3 mediates radioresistance of esophageal cancer cells through suppressing MAPK and AKT signaling.BMC cancer · 2024Article
- LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells.The EMBO journal · 2024Article
- P38 MAPK and Radiotherapy: Foes or Friends?Cancers · 2023Review
- Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion.Nature communications · 2022Article
- Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance.Journal of cancer research and clinical oncology · 2022Review
- ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Triclosan induces apoptosis in Burkitt lymphoma-derived BJAB cells through caspase and JNK/MAPK pathways.Apoptosis : an international journal on programmed cell death · 2021Article
- Targeting cancer-cell mitochondria and metabolism to improve radiotherapy response.Translational oncology · 2021Review
- Article
- ROCK2 disturbs MKP1 expression to promote invasion and metastasis in hepatocellular carcinoma.American journal of cancer research · 2020Article
- An integrated stress response via PKR suppresses HER2+ cancers and improves trastuzumab therapy.Nature communications · 2019Article
- Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance.Cancer letters · 2019Review
- CPT1A/2-Mediated FAO Enhancement-A Metabolic Target in Radioresistant Breast Cancer.Frontiers in oncology · 2019Article
- Cancer-adipose tissue interaction and fluid flow synergistically modulate cell kinetics, HER2 expression, and trastuzumab efficacy in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2018Article
- Role of metabolism in cancer cell radioresistance and radiosensitization methods.Journal of experimental & clinical cancer research : CR · 2018Review
- Cross-cancer Prediction: A Novel Machine Learning Approach to Discover Molecular Targets for Development of Treatments for Multiple Cancers.Cancer informatics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The MAPK phosphatase MKP1 (DUSP1) is overexpressed in many human cancers, including chemoresistant and radioresistant breast cancer cells, but its functional contributions in these settings are unclear. Here, we report that after cell irradiation, MKP1 translocates into mitochondria, where it prevents apoptotic induction by limiting accumulation of phosphorylated active forms of the stress kinase JNK. Increased levels of mitochondrial MKP1 after irradiation occurred in the mitochondrial inner membrane space. Notably, cell survival regulated by mitochondrial MKP1 was responsible for conferring radioresistance in HER2-overexpressing breast cancer cells, due to the fact that MKP1 serves as a major downstream effector in the HER2-activated RAF-MEK-ERK pathway. Clinically, we documented MKP1 expression exclusively in HER2-positive breast tumors, relative to normal adjacent tissue from the same patients. MKP1 overexpression was also detected in irradiated HER2-positive breast cancer stem-like cells (HER2(+)/CD44(+)/CD24(-/low)) isolated from a radioresistant breast cancer cell population after long-term radiation treatment. MKP1 silencing reduced clonogenic survival and enhanced radiosensitivity in these stem-like cells. Combined inhibition of MKP1 and HER2 enhanced cell killing in breast cancer. Together, our findings identify a new mechanism of resistance in breast tumors and reveal MKP1 as a novel therapeutic target for radiosensitization.
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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.