ArticleNature communications2015
A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Merlin deficiency supports an immunosuppressive milieu in breast cancer.Cell death discovery · 2026Article
- FXR1-Directed Alternative Splicing of MK5 Drives Hepatocellular Carcinoma Progression by Activating GSK3β Signaling.Cancer science · 2026Article
- Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets.Nature communications · 2025Article
- Development of Novel Bioluminescent Biosensors Monitoring the Conformation and Activity of the Merlin Tumour Suppressor.International journal of molecular sciences · 2024Article
- Article
- Missense variant interaction scanning reveals a critical role of the FERM domain for tumor suppressor protein NF2 conformation and function.Life science alliance · 2023Article
- Article
- Mechanisms of portal vein tumour thrombus formation and development in patients with hepatocellular carcinoma.Journal of cellular and molecular medicine · 2023Review
- Review
- Deletion ofCells · 2023Article
- Article
- Review
- QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer.Journal of molecular cell biology · 2021Article
- LINC01348 suppresses hepatocellular carcinoma metastasis through inhibition of SF3B3-mediated EZH2 pre-mRNA splicing.Oncogene · 2021Article
- Ascorbic Acid Inhibits Liver Cancer Growth and MetastasisFrontiers in pharmacology · 2021Article
- Alternative Splicing in Hepatocellular Carcinoma.Cellular and molecular gastroenterology and hepatology · 2020Review
- Clinical and functional significance of CHK1-S, an alternatively spliced isoform of the CHK1 gene, in hepatocellular carcinoma.Journal of Cancer · 2020Article
- Long-Read RNA Sequencing Identifies Alternative Splice Variants in Hepatocellular Carcinoma and Tumor-Specific Isoforms.Hepatology (Baltimore, Md.) · 2019Article
- Prognostic index of aberrant mRNA splicing profiling acts as a predictive indicator for hepatocellular carcinoma based on TCGA SpliceSeq data.International journal of oncology · 2019Article
- The natural compound neobractatin inhibits tumor metastasis by upregulating the RNA-binding-protein MBNL2.Cell death & disease · 2019Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Merlin, which is encoded by the tumour suppressor gene Nf2, plays a crucial role in tumorigenesis and metastasis. However, little is known about the functional importance of Merlin splicing forms. In this study, we show that Merlin is present at low levels in human hepatocellular carcinoma (HCC), particularly in metastatic tumours, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 ((Δ2-4)Merlin) is amplified in HCC and portal vein tumour thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that (Δ2-4)Merlin interferes with the capacity of wild-type Merlin to bind β-catenin and ERM, and it is expressed in the cytoplasm rather than at the cell surface. Furthermore, (Δ2-4)Merlin overexpression increases the expression levels of β-catenin and stemness-related genes, induces the epithelium-mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the (Δ2-4)Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.
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