ArticleJournal of experimental & clinical cancer research : CR2017
The acid-sensing ion channel, ASIC2, promotes invasion and metastasis of colorectal cancer under acidosis by activating the calcineurin/NFAT1 axis.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 81 citations in OpenAlex.
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- Ocean acidification induces neuronal hyperexcitation and anxiety-like behaviour in marine medaka via ASIC activation.Fish physiology and biochemistry · 2026Article
- Article
- The role of ASIC2 in glioma progression: implications for prognosis and therapeutic targeting.PeerJ · 2026Article
- Porphyromonas gingivalis extracellular vesicles promotes tumor metastasis in esophageal squamous cell carcinoma by inducing PRKACB/JNK/ NFATC2 axis.Journal of nanobiotechnology · 2025Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- It Is Time to Consider the Lost Battle of Microdamaged Piezo2 in the Context ofInternational journal of molecular sciences · 2025Review
- Novel Shared Heritable Candidate Risk Loci of Breast and Endometrial Cancer-A Swedish Haplotype Genome-Wide Association Study.International journal of molecular sciences · 2025Article
- Low pH induces amiloride-sensitive expression of leukemia inhibitory factor in endometrial cells.The Journal of reproduction and development · 2025Article
- The relationship between acid-sensing ion channel, ASIC2, and oncogenic β-catenin signaling in ovarian cancer.Scientific reports · 2025Article
- Ion-Channel Proteins in the Prepubertal Bitch Reproductive System: The Immunolocalization of ASIC2, ASIC4, and PIEZO2.International journal of molecular sciences · 2025Article
- ASIC3-activated key enzymes of de novo lipid synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells.Cell communication and signaling : CCS · 2024Article
- Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?Pflugers Archiv : European journal of physiology · 2024Review
- LncRNA LUESCC promotes esophageal squamous cell carcinoma by targeting the miR-6785-5p/NRSN2 axis.Cellular and molecular life sciences : CMLS · 2024Article
- Unveiling the hidden risks: albumin-corrected anion gap as a superior marker for cardiovascular mortality in type 2 diabetes: insights from a nationally prospective cohort study.Frontiers in endocrinology · 2024Article
- Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons.Pflugers Archiv : European journal of physiology · 2023Article
- Anticancer Effect of Gallic Acid on Acidity-Induced Invasion of MCF7 Breast Cancer Cells.Nutrients · 2023Article
- Sodium channels and the ionic microenvironment of breast tumours.The Journal of physiology · 2023Article
- Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro.Cancers · 2023Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe tumor acidic microenvironment, a common biochemical event in solid tumors, offers evolutional advantage for tumors cells and even enhances their aggressive phenotype. However, little is known about the molecular mechanism underlying the acidic microenvironment-induced invasion and metastasis.
methodsWe examined the expression of the acid-sending ion channel (ASIC) family members after acidic exposure using RT-PCR and immunofluoresence. Gene manipulation was applied to reveal the potential of ASIC2 on invasion, proliferation, colony formation of colorectal cancer (CRC). We assessed the in vivo tumor growth by subcutaneous transplantation and metastasis by spleen xenografts. Chromatin immunoprecipitation-sequencing was used to uncover the binding sites of NFAT1. Finally, we examined the expression of ASIC2 in CRC tissues using immunohistochemistry.
resultsAcidic exposure led to up-regulation of the acid-sensing ion channel, ASIC2, in colorectal cancer (CRC) cells. ASIC2 overexpression in CRC cell lines, SW480 and HCT116, significantly enhanced cell proliferation in vitro and in vivo, while ASIC2 knockdown had the reverse effect. Importantly, ASIC2 promoted CRC cell invasion under acidosis in vitro and liver metastasis in vivo. Mechanistically, ASIC2 activated the calcineurin/NFAT1 signaling pathway under acidosis. Inhibition of the calcineurin/NFAT pathway by cyclosporine A (CsA) profoundly attenuated ASIC2-induced invasion under acidosis. ChIP-seq assay revealed that the nuclear factor, NFAT1, binds to genes clustered in pathways involved in Rho GTPase signaling and calcium signaling. Furthermore, immunohistochemistry showed that ASIC2 expression is increased in CRC samples compared to that in adjacent tissues, and ASIC2 expression correlates with T-stage, distant metastasis, recurrence, and poor prognosis.
conclusionASIC2 promotes metastasis of CRC cells by activating the calcineurin/NFAT1 pathway under acidosis and high expression of ASIC2 predicts poor outcomes of patients with CRC.
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