ArticleOncogene2021
PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Combined analysis of metabolomics and transcriptomics reveals new indicators for the diagnosis and prognosis of colorectal cancer.Contemporary oncology (Poznan, Poland) · 2026Article
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Research on the correlation and potential mechanism of PKCδ expression with efficacy and prognosis in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Article
- SGLT2 inhibitors and mortality in diabetic cancer patients: cardioprotective and anticancer effects.European heart journal. Cardiovascular pharmacotherapy · 2025Article
- Synergistic inhibitory effect of atmospheric pressure plasma and berberine on non‑small cell lung cancer cells via inducing apoptosis.Molecular biology reports · 2024Article
- Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury.Molecular medicine reports · 2024Article
- Impact of Drug-Mediated Inhibition of Intestinal Transporters on Nutrient and Endogenous Substrate Disposition…an Afterthought?Pharmaceutics · 2024Review
- Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice.Frontiers in pharmacology · 2023Review
- Dual data and motif clustering improves the modeling and interpretation of phosphoproteomic data.Cell reports methods · 2022Article
- Bruceine H Mediates EGFR-TKI Drug Persistence in NSCLC by Notch3-Dependent β-Catenin Activating FOXO3a Signaling.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKCδ-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKCδ/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKCδ/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
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