ArticleThe Journal of biological chemistry2014
Small molecule-facilitated degradation of ANO1 protein: a new targeting approach for anticancer therapeutics.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 83 citations in OpenAlex.
- An All-Optical Approach to Probe Chloride Transport with a Bright ChlorON.bioRxiv : the preprint server for biology · 2026Article
- Blockade of calcium-activated chloride channel ANO1 ameliorates ionizing radiation-induced intestinal injury.Journal of advanced research · 2026Article
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- p90RSK pathway inhibition synergizes with cisplatin in TMEM16A overexpressing head and neck cancer.BMC cancer · 2024Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- TRPV3-ANO1 interaction positively regulates wound healing in keratinocytes.Communications biology · 2023Article
- Aberrations in ion channels interacting with lipid metabolism and epithelial-mesenchymal transition in esophageal squamous cell carcinoma.Frontiers in molecular biosciences · 2023Article
- Role of ANO1 in tumors and tumor immunity.Journal of cancer research and clinical oncology · 2022Review
- TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Reduced Expression of TMEM16A Impairs Nitric Oxide-Dependent ClFrontiers in cellular neuroscience · 2022Article
- Discovery of 4-arylthiophene-3-carboxylic acid as inhibitor of ANO1 and its effect as analgesic agent.Acta pharmaceutica Sinica. B · 2021Article
- Simvastatin inhibits oral squamous cell carcinoma by targeting TMEM16A CaJournal of cancer research and clinical oncology · 2021Article
- The CaActa pharmaceutica Sinica. B · 2021Review
- ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma.Cancers · 2021Article
- ANO1 regulates the maintenance of stemness in glioblastoma stem cells by stabilizing EGFRvIII.Oncogene · 2021Article
- Article
- Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers.Molecules (Basel, Switzerland) · 2020Article
- Drug development in targeting ion channels for brain edema.Acta pharmacologica Sinica · 2020Article
- Cyst growth in ADPKD is prevented by pharmacological and genetic inhibition of TMEM16A in vivo.Nature communications · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ANO1, a calcium-activated chloride channel, is highly expressed and amplified in human cancers and is a critical survival factor in these cancers. The ANO1 inhibitor CaCCinh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of action remains elusive. We explored the mechanism behind the inhibitory effect of CaCCinh-A01 on cell proliferation using a combined experimental and in silico approach. We show that inhibition of ANO1 function is not sufficient to diminish proliferation of ANO1-dependent cancer cells. We report that CaCCinh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCCinh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCCinh-A01-resistant cell pools was not affected by CaCCinh-A01 as compared with the parental cells. Consistently, CaCCinh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCCinh-A01, indicating that CaCCinh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Furthermore, we employed in silico methods to elucidate novel biological functions of ANO1 inhibitors. Specifically, we derived a pharmacophore model to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-dependent cell proliferation. In summary, our data demonstrate that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as a channel. Our results provide an impetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting approach for antitumor therapy in ANO1-amplified cancers.
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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.