ArticleOncotarget2016
Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- The metabolic addiction of cancer stem cells.Frontiers in oncology · 2022Pooled it
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- PTTG1-DLX2 axis drives malignant progression of lung adenocarcinoma by activating the WNT/β-catenin signaling pathway.Translational cancer research · 2026Article
- Review
- Decoding chromosomal instability insights in CRC by integrating omics and patient-derived organoids.Journal of experimental & clinical cancer research : CR · 2025Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors.Cell communication and signaling : CCS · 2024Review
- Factors Determining Epithelial-Mesenchymal Transition in Cancer Progression.International journal of molecular sciences · 2024Review
- Overexpression of circular RNA hsa_circ_0008621 facilitates colorectal cancer progression and predicts poor prognosis.Annals of gastroenterological surgery · 2024Article
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Spatial and Temporal Relationship between Epithelial-Mesenchymal Transition (EMT) and Stem Cells in Cancer.Clinical chemistry · 2024Article
- Oxidative stress regulation and related metabolic pathways in epithelial-mesenchymal transition of breast cancer stem cells.Stem cell research & therapy · 2023Review
- Regulation of glucose and glutamine metabolism to overcome cisplatin resistance in intrahepatic cholangiocarcinoma.BMB reports · 2023Article
- Role of c-Myc in lung cancer: Progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2023Article
- The novel epithelial-mesenchymal transition-related proteins and their therapeutic targets in cholangiocarcinoma: a narrative review.Journal of gastrointestinal oncology · 2023Review
- Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.International journal of molecular sciences · 2023Review
- Effects of Dlx2 overexpression on the genes associated with the maxillary process in the early mouse embryo.Frontiers in genetics · 2023Article
- Metabolic Reprogramming of Castration-Resistant Prostate Cancer Cells as a Response to Chemotherapy.Metabolites · 2022Article
- The Epithelial-Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most cancer cells depend on enhanced glucose and glutamine (Gln) metabolism for growth and survival. Oncogenic metabolism provides biosynthetic precursors for nucleotides, lipids, and amino acids; however, its specific roles in tumor progression are largely unknown. We previously showed that distal-less homeobox-2 (Dlx-2), a homeodomain transcription factor involved in embryonic and tumor development, induces glycolytic switch and epithelial-mesenchymal transition (EMT) by inducing Snail expression. Here we show that Dlx-2 also induces the expression of the crucial Gln metabolism enzyme glutaminase (GLS1), which converts Gln to glutamate. TGF-β and Wnt induced GLS1 expression in a Dlx-2-dependent manner. GLS1 shRNA (shGLS1) suppressed in vivo tumor metastasis and growth. Inhibition of Gln metabolism by shGLS1, Gln deprivation, and Gln metabolism inhibitors (DON, 968 and BPTES) prevented Dlx-2-, TGF-β-, Wnt-, and Snail-induced EMT and glycolytic switch. Finally, shDlx-2 and Gln metabolism inhibition decreased Snail mRNA levels through p53-dependent upregulation of Snail-targeting microRNAs. These results demonstrate that the Dlx-2/GLS1/Gln metabolism axis is an important regulator of TGF-β/Wnt-induced, Snail-dependent EMT, metastasis, and glycolytic switch.
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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.