ArticleJournal of experimental & clinical cancer research : CR2024
Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Human airway organoids for bacterial-host interaction studies: methods, insights and translational promise.Thorax · 2026Review
- Machine learning-based prognostic model and single-cell transcriptomic integration for identifying brain metastasis-associated malignant subpopulations and potential therapeutic targets in lung adenocarcinoma.Cancer cell international · 2026Article
- Targeting MET in non-small cell lung cancer brain metastases: from molecular mechanism to precision therapy.Journal of translational medicine · 2026Review
- A monoclonal antibody W1 blocks mesothelin-mediated tumor progression.Molecular therapy. Oncology · 2026Article
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
- ORANGE: a machine learning approach for modeling tissue-specific aging from transcriptomic data.Briefings in bioinformatics · 2026Article
- From Cerebrovascular Injury to Brain Cancer: The Role of Blood-Brain Barrier Dysfunction.Biomedicines · 2026Review
- MET alterations are enriched in lung adenocarcinoma brain metastases, defining a distinct biologic subtype.The Journal of clinical investigation · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- circ_PPAPDC1A is Associated with Brain Metastasis of Non-Small-Cell Lung Cancer via the miR-30a-3p/SPOCK1 Pathway.Annals of surgical oncology · 2026Article
- Savolitinib in brain and leptomeningeal metastases from non-small cell lung cancer: a case report.Frontiers in oncology · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- CD146Theranostics · 2026Article
- Integrative single-cell and bulk RNA sequencing unravels the role of ACTN1 in promoting lung cancer with brain metastasis and epidermal growth factor receptor-tyrosine kinase inhibitor resistance.Frontiers in cell and developmental biology · 2026Article
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations.Molecular biomedicine · 2025Review
- Comprehensive single-cell transcriptome landscape of metastatic colorectal cancer identifies budding-potential cells and their interactions with cancer-associated fibroblasts.NPJ precision oncology · 2025Article
- Probing Nanomechanics by Direct Indentation Using Nanoendoscopy-AFM Reveals the Nuclear Elasticity Transition in Cancer Cells.ACS applied nano materials · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBrain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown.
methodsThe expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies.
resultsMSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice.
conclusionsOur results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.
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