ArticleOncotarget2018
High salt induces P-glycoprotein mediated treatment resistance in breast cancer cells through store operated calcium influx.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Sodium accumulation in breast cancer predicts malignancy and treatment response.British journal of cancer · 2022Trial
- Smart mesoporous silica nanoparticles for precision cancer therapy: Tumor targeting and stimuli-responsive controlled release.Smart molecules : open access · 2026Review
- Review
- Sodium regulates PLC and IPPhysiological reports · 2023Article
- Dual Anticancer and Antibacterial Properties of Silica-Based Theranostic Nanomaterials Functionalized with Coumarin343, Folic Acid and a Cytotoxic Organotin(IV) Metallodrug.Pharmaceutics · 2023Article
- Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein-In Silico and In Vitro Evidence.Molecules (Basel, Switzerland) · 2022Article
- The modulatory effect of high salt on immune cells and related diseases.Cell proliferation · 2022Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Cancer Salt Nostalgia.Cells · 2021Article
- Ex Vivo High Salt Activated Tumor-Primed CD4+T Lymphocytes Exert a Potent Anti-Cancer Response.Cancers · 2021Article
- SIKs suppress tumor function and regulate drug resistance in breast cancer.American journal of cancer research · 2021Article
- Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated CaJournal of biomedical science · 2020Article
- Article
- Perplexing Role of P-Glycoprotein in Tumor Microenvironment.Frontiers in oncology · 2020Review
- Article
- Sodium homeostasis in the tumour microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Article
- Review
- Downregulated Salt-inducible Kinase 3 Expression Promotes Chemoresistance in Serous Ovarian Cancer via the ATP-binding Cassette Protein ABCG2.Journal of Cancer · 2019Article
- Store-Operated CaInternational journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 cells with high salt induced an enhanced intracellular calcium intensity, which was significantly decreased by store operated calcium entry (SOCE) inhibitor co-treatment. Further, high salt induced P-glycoprotein (P-gp) mediated paclitaxel drug resistance in breast cancer cells. Murine tumor studies demonstrated that injection of MCF-7 cells cultured in high salt, exerted higher tumorigenicity compared to the basal cultured counterpart. Knock down of SIK3 by specific shRNA inhibited tumorigenicty, expression of SOCE regulators and P-gp activity, suggesting SIK3 is an upstream mediator of SOCE induced calcium influx. Furthermore, small molecule inhibitor, prostratin, exerted anti-tumor effect in murine models through SIK3 inhibition. Taken together, we conclude that SIK3 is an upstream regulator of store operated calcium entry proteins, Orai1 and STIM1, and mediates high salt induced inflammatory cytokine responses and P-gp mediated drug resistance. Therefore, small molecule inhibitors, such as prostratin, could offer novel anti-cancer approaches.
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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.