ArticleCancer letters2016
ASCT2 (SLC1A5) is an EGFR-associated protein that can be co-targeted by cetuximab to sensitize cancer cells to ROS-induced apoptosis.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Beyond the membrane: rethinking EGFR signaling in physiology and cancer.Cellular and molecular life sciences : CMLS · 2026Review
- Integrative Transcriptomic and Genetic Analysis PrioritizesClinical, cosmetic and investigational dermatology · 2026Article
- The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression.Frontiers in bioscience (Landmark edition) · 2025Review
- Integrating transcriptomic and metabolomic analyses to characterize the potential function of SLC1A5 in thyroid cancer.BMC cancer · 2025Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- CRISPR/Cas9 mediated ENT2 gene knockout altered purine catabolic pathway and induced apoptosis in colorectal cell lines.PloS one · 2025Article
- Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma.Science advances · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- DRP1 inhibition-mediated mitochondrial elongation abolishes cancer stemness, enhances glutaminolysis, and drives ferroptosis in oral squamous cell carcinoma.British journal of cancer · 2024Article
- Inhibition of thioredoxin-1 enhances the toxicity of glycolysis inhibitor 2-deoxyglucose by downregulating SLC1A5 expression in colorectal cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Distinct roles and molecular mechanisms of nicotine and benzo(a)pyrene in ferroptosis of lung adenocarcinoma and lung squamous cell carcinoma.Tobacco induced diseases · 2024Article
- Membrane transporters in cell physiology, cancer metabolism and drug response.Disease models & mechanisms · 2023Review
- Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma.Molecular cancer therapeutics · 2023Article
- IncreasedExperimental and therapeutic medicine · 2023Article
- Blocking EREG/GPX4 Sensitizes Head and Neck Cancer to Cetuximab through Ferroptosis Induction.Cells · 2023Article
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- Article
- Relationships betweenComparative medicine · 2021Article
- Review
- The role of the glutamine transporter ASCT2 in antineoplastic therapy.Cancer chemotherapy and pharmacology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Therapeutic targeting of ASCT2, a glutamine transporter that plays a major role in glutamine uptake in cancer cells, is challenging because ASCT2 also has a biological role in normal tissues. In this study, we report our novel finding that ASCT2 is physically associated in a molecular complex with epidermal growth factor receptor (EGFR), which is often overexpressed in human head and neck squamous cell carcinoma (HNSCC). Furthermore, we found that ASCT2 can be co-targeted by cetuximab, an EGFR antibody approved for treating metastatic HNSCC. We demonstrated that cetuximab downregulated ASCT2 in an EGFR expression-dependent manner via cetuximab-mediated EGFR endocytosis. Downregulation of ASCT2 by cetuximab led to decreased intracellular uptake of glutamine and subsequently a decreased glutathione level. Cetuximab thereby sensitized HNSCC cells to reactive oxygen species (ROS)-induced apoptosis and, importantly, it is independent of effective inhibition of EGFR downstream signaling by cetuximab. In contrast, knockdown of EGFR by siRNA or inhibition of EGFR kinase with gefitinib, an EGFR kinase inhibitor, failed to sensitize HNSCC cells to ROS-induced apoptosis. Our findings support a novel therapeutic strategy for EGFR-overexpressing and cetuximab-resistant cancers by combining cetuximab with an oxidative therapy.
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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.