ArticleCell death discovery2023
MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 12 citations in OpenAlex.
- Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer.Nature communications · 2026Article
- Review
- Review
- Inhibition of LDHB triggers DNA damage and increases cisplatin sensitivity in pleural mesothelioma.Oncogenesis · 2025Article
- Malignant peritoneal mesothelioma interactome with 417 novel protein-protein interactions.BJC reports · 2024Article
- BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma.JTO clinical and research reports · 2024Article
- Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy.Molecules (Basel, Switzerland) · 2023Review
- Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
Malignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity. Suppression of MAPK signaling by clinically approved MEK inhibitors (MEKi) elicits PARP1 to protect MPM cells from the cytotoxic effects of MAPK pathway blockage. Mechanistically, MEKi induces impairment of homologous recombination (HR) repair proficiency and mitochondrial metabolic activity, which is counterbalanced by pleiotropic PARP1. Consequently, the combination of MEK with PARP inhibitors enhances apoptotic cell death in vitro and in vivo that occurs through coordinated upregulation of cytotoxic ROS in MPM cells, suggesting a mechanism-based, readily translatable strategy to treat this daunting disease. Collectively, our studies uncover a previously unrecognized scenario that hyperactivation of the MAPK pathway is an essential feature of MPM and provide unprecedented evidence that MAPK signaling cooperates with PARP1 to homeostatically maintain ROS levels and escape ROS-mediated apoptosis.
Identifiers
What OpenQuestion holds
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.