ArticleCancer research2014
Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- Modeling Malignant Mesothelioma in Genetically Engineered Mice.Current protocols · 2025Article
- Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma.Carcinogenesis · 2022Article
- Epigenetic Regulation by Polycomb Complexes from Drosophila to Human and Its Relation to Communicable Disease Pathogenesis.International journal of molecular sciences · 2022Review
- Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability.Cancers · 2022Article
- Expression characteristics of long non-coding RNA in colon adenocarcinoma and its potential value for judging the survival and prognosis of patients: bioinformatics analysis based on The Cancer Genome Atlas database.Journal of gastrointestinal oncology · 2022Article
- Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Tumors by Restricting Downstream Hedgehog and Wnt Signaling.Molecular cancer research : MCR · 2022Article
- KRAS signaling in malignant pleural mesothelioma.EMBO molecular medicine · 2022Article
- Promising therapeutic potential of tumor suppressor microRNAs for malignant pleural mesothelioma.Journal of cancer metastasis and treatment · 2022Article
- Review
- The pathogenesis of mesothelioma is driven by a dysregulated translatome.Nature communications · 2021Article
- Mouse models for mesothelioma drug discovery and development.Expert opinion on drug discovery · 2021Review
- Role of microRNAs in Lung Carcinogenesis Induced by Asbestos.Journal of personalized medicine · 2021Review
- Preclinical Models of Malignant Mesothelioma.Frontiers in oncology · 2020Review
- Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma.Therapeutic advances in medical oncology · 2020Review
- Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future.Frontiers in oncology · 2020Review
- Article
- Inactivation ofCancer research · 2019Article
- Role of RNA-binding protein 5 in the diagnosis and chemotherapeutic response of lung cancer.Oncology letters · 2019Review
- Inactivation of Tp53 and Pten drives rapid development of pleural and peritoneal malignant mesotheliomas.Journal of cellular physiology · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Malignant mesothelioma is a highly aggressive, asbestos-related cancer frequently marked by mutations of both NF2 and CDKN2A. We demonstrate that germline knockout of one allele of each of these genes causes accelerated onset and progression of asbestos-induced malignant mesothelioma compared with asbestos-exposed Nf2(+/-) or wild-type mice. Ascites from some Nf2(+/-);Cdkn2a(+/-) mice exhibited large tumor spheroids, and tail vein injections of malignant mesothelioma cells established from these mice, but not from Nf2(+/-) or wild-type mice, produced numerous tumors in the lung, suggesting increased metastatic potential of tumor cells from Nf2(+/-);Cdkn2a(+/-) mice. Intraperitoneal injections of malignant mesothelioma cells derived from Nf2(+/-);Cdkn2a(+/-) mice into severe combined immunodeficient mice produced tumors that penetrated the diaphragm and pleural cavity and harbored increased cancer stem cells (CSC). Malignant mesothelioma cells from Nf2(+/-);Cdkn2a(+/-) mice stained positively for CSC markers and formed CSC spheroids in vitro more efficiently than counterparts from wild-type mice. Moreover, tumor cells from Nf2(+/-);Cdkn2a(+/-) mice showed elevated c-Met expression/activation, which was partly dependent on p53-mediated regulation of miR-34a and required for tumor migration/invasiveness and maintenance of the CSC population. Collectively, these studies demonstrate in vivo that inactivation of Nf2 and Cdkn2a cooperate to drive the development of highly aggressive malignant mesotheliomas characterized by enhanced tumor spreading capability and the presence of a CSC population associated with p53/miR-34a-dependent activation of c-Met. These findings suggest that cooperativity between losses of Nf2 and Cdkn2a plays a fundamental role in driving the highly aggressive tumorigenic phenotype considered to be a hallmark of malignant mesothelioma.
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