ArticleNature genetics2022
The NALCN channel regulates metastasis and nonmalignant cell dissemination.
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
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- Defining the mucosal ecosystem: epithelial-mesenchymal interdependence in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis.Oncogene · 2025Article
- Multiplex characterization of circulating tumor cells from ductal carcinoma in situ patients suggests early tumor dissemination.Cancer letters · 2025Article
- Primary and secondary metastatic dissemination: multiple routes to cancer-related death.Molecular cancer · 2025Review
- A Robust Association Test Leveraging Unknown Genetic Interactions: Application to Cystic Fibrosis Lung Disease.Genetic epidemiology · 2025Article
- Circulating tumor cells and clusters as liquid biomarkers for the diagnosis and prognosis of neuroblastoma.BMC cancer · 2025Article
- Genomic Signatures of Recurrence After Resection of Early-Stage Node-Negative Colon Cancer.Annals of surgical oncology · 2025Article
- SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.Journal of cellular physiology · 2025Article
- Persistent and novel changes in plasma microRNA profiles in patients with non-small cell lung cancer following tumour resection.Translational lung cancer research · 2025Article
- Personalized prediction of anticancer potential of non-oncology drugs through learning from genome derived molecular pathways.NPJ precision oncology · 2025Article
- NALCN expression is down-regulated and associated with immune infiltration in gastric cancer.Frontiers in immunology · 2025Article
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- Parahydrogen-enhanced pH measurements using [1-The Analyst · 2024Article
- Putative epithelial-mesenchymal transitions during salamander limb regeneration: Current perspectives and future investigations.Annals of the New York Academy of Sciences · 2024Review
- How much do we know about the metastatic process?Clinical & experimental metastasis · 2024Review
- A novel NaOncogene · 2024Article
- Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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20 authors at 8 institutions in 2 countries.
Funding
Abstract
We identify the sodium leak channel non-selective protein (NALCN) as a key regulator of cancer metastasis and nonmalignant cell dissemination. Among 10,022 human cancers, NALCN loss-of-function mutations were enriched in gastric and colorectal cancers. Deletion of Nalcn from gastric, intestinal or pancreatic adenocarcinomas in mice did not alter tumor incidence, but markedly increased the number of circulating tumor cells (CTCs) and metastases. Treatment of these mice with gadolinium-a NALCN channel blocker-similarly increased CTCs and metastases. Deletion of Nalcn from mice that lacked oncogenic mutations and never developed cancer caused shedding of epithelial cells into the blood at levels equivalent to those seen in tumor-bearing animals. These cells trafficked to distant organs to form normal structures including lung epithelium, and kidney glomeruli and tubules. Thus, NALCN regulates cell shedding from solid tissues independent of cancer, divorcing this process from tumorigenesis and unmasking a potential new target for antimetastatic therapies.
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