ArticleOncogene2016
A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- EML4-ALK fusion rewires transcriptomic, miRNA, and CAF-associated programs in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- "Friends or foes": a new perspective of tumour metabolic transcriptional modification.Cell death & disease · 2025Review
- ALK fusion promotes metabolic reprogramming of cancer cells by transcriptionally upregulating PFKFB3.Oncogene · 2022Article
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.Thoracic cancer · 2021Article
- Metabolic Phenotypes, Dependencies, and Adaptation in Lung Cancer.Cold Spring Harbor perspectives in medicine · 2021Review
- Methylation-associated silencing of miR-9-1 promotes nasopharyngeal carcinoma progression and glycolysis via HK2.Cancer science · 2021Article
- Review
- SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis.Nature communications · 2021Article
- Monoamine Oxidase A Inhibits Lung Adenocarcinoma Cell Proliferation by Abrogating Aerobic Glycolysis.Frontiers in oncology · 2021Article
- Shining a light on metabolic vulnerabilities in non-small cell lung cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Prognostic implication of glycolysis related gene signature in non-small cell lung cancer.Journal of Cancer · 2021Article
- Article
- The multi-faceted functioning portrait of LRF/ZBTB7A.Human genomics · 2019Review
- Inhibition of hexokinases holds potential as treatment strategy for rheumatoid arthritis.Arthritis research & therapy · 2019Article
- Crizotinib-induced immunogenic cell death in non-small cell lung cancer.Nature communications · 2019Article
- Neuron-Specific Enolase Is an Independent Prognostic Factor in Resected Lung Adenocarcinoma Patients with Anaplastic Lymphoma Kinase Gene Rearrangements.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Immunometabolism: A new target for improving cancer immunotherapy.Advances in cancer research · 2019Review
- Ovarian Cancer Relies on Glucose Transporter 1 to Fuel Glycolysis and Growth: Anti-Tumor Activity of BAY-876.Cancers · 2018Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
A high rate of aerobic glycolysis is a hallmark of malignant transformation. Accumulating evidence suggests that diverse regulatory mechanisms mediate this cancer-associated metabolic change seen in a wide spectrum of cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein is found in approximately 3-7% of non-small cell lung carcinomas (NSCLC). Molecular evidence and therapeutic effectiveness of FDA-approved ALK inhibitors indicated that EML4-ALK is a driving factor of lung tumorigenesis. A recent clinical study showed that NSCLC harboring EML4-ALK rearrangements displayed higher glucose metabolism compared with EML4-ALK-negative NSCLC. In the current work, we presented evidence that EML4-ALK is coupled to overexpression of hexokinase II (HK2), one of the rate-limiting enzymes of the glycolytic pathway. The link from EML4-ALK to HK2 upregulation is essential for a high rate of glycolysis and proliferation of EML4-ALK-rearranged NSCLC cells. We identified hypoxia-inducible factor 1α (HIF1α) as a key transcription factor to drive HK2 gene expression in normoxia in these cells. EML4-ALK induced hypoxia-independent but glucose-dependent accumulation of HIF1α protein via both transcriptional activation of HIF1α mRNA and the phosphatidylinositol 3 kinase-AKT pathway to enhance HIF1α protein synthesis. The EML4-ALK-mediated upregulation of HIF1α, HK2 and glycolytic metabolism was also highly active in vivo as demonstrated by fluorodeoxyglucose-positron emission tomography imaging of xenografts grown from EML4-ALK-positive NSCLC cells. Our data reveal a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC.
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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.