ArticleProceedings of the National Academy of Sciences of the United States of America2012
Selective requirement for Mediator MED23 in Ras-active lung cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Splice isoform-perturbation coupled to single cell transcriptome profiling reveals functions of microexons in neurogenesis and autism-linked pathways.Nature communications · 2026Article
- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mediator complex subunit MED23 dampens antiviral innate immunity by restricting RIG-I expression.PLoS biology · 2025Article
- Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.Nature communications · 2025Article
- Article
- Profiling nuclear cysteine ligandability and effects on nuclear localization using proximity labeling-coupled chemoproteomics.Cell chemical biology · 2024Article
- Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis.British journal of cancer · 2024Article
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- HPV-18 E7 Interacts with Elk-1 Leading to Elevation of the Transcriptional Activity of Elk-1 in Cervical Cancer.Biomolecules & therapeutics · 2022Article
- Integration of radiogenomic features for early prediction of pathological complete response in patients with triple-negative breast cancer and identification of potential therapeutic targets.Journal of translational medicine · 2022Article
- Med23 supports angiogenesis and maintains vascular integrity through negative regulation of angiopoietin2 expression.Communications biology · 2022Article
- What do Transcription Factors Interact With?Journal of molecular biology · 2021Review
- Review
- Mediator Med23 Regulates Adult Hippocampal Neurogenesis.Frontiers in cell and developmental biology · 2020Article
- Mediator MED23 regulates inflammatory responses and liver fibrosis.PLoS biology · 2019Article
- Article
- Novel mutation in theClinical case reports · 2019Article
- Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23.Nature communications · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
K-RAS-activating mutations occur frequently in non-small cell lung cancer, leading to aberrant activation of the Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23 deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. The transcription factor ELK1, which is phosphorylated by MAPK for relaying Ras signaling to MED23, also was required for the Ras-driven oncogenesis. Transcriptome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell-cycle and -proliferation functions to support the Ras dependency. Furthermore, MED23 was up-regulated by Ras transformation in correlation with the strength of Ras signaling as indicated by the ELK1 phosphorylation level and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicted better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the "Ras-addiction" of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer.
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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.