ArticleOncotarget2016
Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Merlin deficiency supports an immunosuppressive milieu in breast cancer.Cell death discovery · 2026Article
- Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse.World journal of stem cells · 2025Review
- Morphological control of merlin-Rac antagonism in proliferation-promoting signaling.Science signaling · 2025Article
- Repeat DNA methylation is modulated by adherens junction signaling.Communications biology · 2024Article
- Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Research progress in breast cancer stem cells: characterization and future perspectives.American journal of cancer research · 2022Review
- Cancer‑associated fibroblast‑derived LRRC15 promotes the migration and invasion of triple‑negative breast cancer cells via Wnt/β‑catenin signalling pathway regulation.Molecular medicine reports · 2022Article
- The Role of the Spinal Wnt Signaling Pathway in HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2020Review
- Merlin regulates signaling events at the nexus of development and cancer.Cell communication and signaling : CCS · 2020Review
- Long non-coding RNA KDM5B anti-sense RNA 1 enhances tumor progression in non-small cell lung cancer.Journal of clinical laboratory analysis · 2020Article
- MicroRNA-216a suppresses the proliferation and migration of human breast cancer cells via the Wnt/β-catenin signaling pathway.Oncology reports · 2019Article
- Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition.International journal of molecular sciences · 2019Review
- miR-30a inhibits breast cancer progression through the Wnt/β-catenin pathway.International journal of clinical and experimental pathology · 2019Article
- The ERM family member Merlin is required for endometrial gland morphogenesis.Developmental biology · 2018Article
- Deficiency of tumor suppressor Merlin facilitates metabolic adaptation by co-operative engagement of SMAD-Hippo signaling in breast cancer.Carcinogenesis · 2018Article
- The association of NF2 (neurofibromin 2) gene polymorphism and the risk of medulloblastomas.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Article
- Traditional and systems biology based drug discovery for the rare tumor syndrome neurofibromatosis type 2.PloS one · 2018Article
- Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers.Cancer research · 2017Article
- Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target.EBioMedicine · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The expression of the tumor suppressor Merlin is compromised in nervous system malignancies due to genomic aberrations. We demonstrated for the first time, that in breast cancer, Merlin protein expression is lost due to proteasome-mediated elimination. Immunohistochemical analysis of tumor tissues from patients with metastatic breast cancer revealed characteristically reduced Merlin expression. Importantly, we identified a functional role for Merlin in impeding breast tumor xenograft growth and reducing invasive characteristics. We sought to determine a possible mechanism by which Merlin accomplishes this reduction in malignant activity. We observed that breast and pancreatic cancer cells with loss of Merlin show an aberrant increase in the activity of β-catenin concomitant with nuclear localization of β-catenin. We discovered that Merlin physically interacts with β-catenin, alters the sub-cellular localization of β-catenin, and significantly reduces the protein levels of β-catenin by targeting it for degradation through the upregulation of Axin1. Consequently, restoration of Merlin inhibited β-catenin-mediated transcriptional activity in breast and pancreatic cancer cells. We also present evidence that loss of Merlin sensitizes tumor cells to inhibition by compounds that target β-catenin-mediated activity. Thus, this study provides compelling evidence that Merlin reduces the malignant activity of pancreatic and breast cancer, in part by suppressing the Wnt/β-catenin pathway. Given the potent role of Wnt/β-catenin signaling in breast and pancreatic cancer and the flurry of activity to test β-catenin inhibitors in the clinic, our findings are opportune and provide evidence for Merlin in restraining aberrant activation of Wnt/β-catenin signaling.
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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.