ArticleNature communications2022
A non-catalytic scaffolding activity of hexokinase 2 contributes to EMT and metastasis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- TRIM32-mediated ubiquitination of STING promotes glycolysis and tumor progression.Cell death and differentiation · 2026Article
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- FAM83D facilitates EMT and metastasis of cervical cancer via interaction with GSK3β and inactivation of GSK3β/stabilization of Snail signaling.Biology direct · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Role of Glycolysis and Nitric Oxide Pathway Crosstalk in Macrophages in Atherosclerosis.Current medicinal chemistry · 2026Review
- Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production.Nature metabolism · 2026Article
- Regulation of drug resistance in bladder urothelial carcinoma by tumor aerobic glycolysis.Journal of translational medicine · 2025Review
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Dysregulated Expression of Canonical and Non-Canonical Glycolytic Enzyme Isoforms in Peripheral Blood from Subjects with Alcohol Use Disorder and from Individuals with Acute Alcohol Consumption.Antioxidants (Basel, Switzerland) · 2025Article
- Hexokinase 2 is an RNA-binding protein that regulates mRNA translation independently of glycolysis and induces melanoma cell proliferation.PLoS biology · 2025Article
- CDH3 promotes the progression of lung adenocarcinoma through driving epithelial-mesenchymal transition progress.Journal of translational medicine · 2025Article
- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- Src inhibition potentiates MCL-1 antagonist activity in acute myeloid leukemia.Signal transduction and targeted therapy · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- The Potential of Nanotechnology in Anti-cancer Drug to Regulate Nrf2 Signaling for Cancer Therapeutic Purposes.Current medicinal chemistry · 2025Review
- Control of Snail1 protein stability by post-translational modifications: the basis for a complex regulation of Snail1 function.International journal of biological sciences · 2025Review
- Characterizing hub biomarkers for metabolic-induced endothelial dysfunction and unveiling their regulatory roles in EndMT through RNA sequencing and machine learning approaches.Frontiers in cardiovascular medicine · 2025Article
- CHML regulates migration and invasion in hepatocellular carcinoma via transcriptional and metabolic reprogramming.Frontiers in oncology · 2025Article
- Moonlighting Proteins: Unveiling Their Multifunctionality in Metabolic Regulation and Drug Discovery.Current drug metabolism · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hexokinase 2 (HK2), which catalyzes the first committed step in glucose metabolism, is induced in cancer cells. HK2's role in tumorigenesis has been attributed to its glucose kinase activity. Here, we describe a kinase independent HK2 activity, which contributes to metastasis. HK2 binds and sequesters glycogen synthase kinase 3 (GSK3) and acts as a scaffold forming a ternary complex with the regulatory subunit of protein kinase A (PRKAR1a) and GSK3β to facilitate GSK3β phosphorylation and inhibition by PKA. Thus, HK2 functions as an A-kinase anchoring protein (AKAP). Phosphorylation by GSK3β targets proteins for degradation. Consistently, HK2 increases the level and stability of GSK3 targets, MCL1, NRF2, and particularly SNAIL. In addition to GSK3 inhibition, HK2 kinase activity mediates SNAIL glycosylation, which prohibits its phosphorylation by GSK3. Finally, in mouse models of breast cancer metastasis, HK2 deficiency decreases SNAIL protein levels and inhibits SNAIL-mediated epithelial mesenchymal transition and metastasis.
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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.