ArticleMolecular pharmaceutics2015
Simultaneously targeting tissue transglutaminase and kidney type glutaminase sensitizes cancer cells to acid toxicity and offers new opportunities for therapeutic intervention.
Article in Molecular pharmaceutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 33 citations in OpenAlex.
- Structural reassignment of compound 968, an allosteric glutaminase inhibitor.Beilstein journal of organic chemistry · 2026Article
- Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer.Nature reviews. Cardiology · 2022Review
- Application of a Fluorescence Anisotropy-Based Assay to Quantify Transglutaminase 2 Activity in Cell Lysates.International journal of molecular sciences · 2022Article
- More Than Meets the Eye Regarding Cancer Metabolism.International journal of molecular sciences · 2021Review
- The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment.Cancers · 2021Review
- Expression of Glutamine Metabolism-Related and Amino Acid Transporter Proteins in Adrenal Cortical Neoplasms and Pheochromocytomas.Disease markers · 2021Article
- Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias.Frontiers in oncology · 2021Review
- Mitochondria Targeting as an Effective Strategy for Cancer Therapy.International journal of molecular sciences · 2020Review
- Dendrimer-conjugated glutaminase inhibitor selectively targets microglial glutaminase in a mouse model of Rett syndrome.Theranostics · 2020Article
- A small molecule regulator of tissue transglutaminase conformation inhibits the malignant phenotype of cancer cells.Oncotarget · 2018Article
- Characterization of the interactions of potent allosteric inhibitors with glutaminase C, a key enzyme in cancer cell glutamine metabolism.The Journal of biological chemistry · 2018Article
- The diamond anniversary of tissue transglutaminase: a protein of many talents.Drug discovery today · 2018Review
- Targeting Glutamine Metabolism for Cancer Treatment.Biomolecules & therapeutics · 2018Review
- Opening up about Tissue Transglutaminase: When Conformation Matters More than Enzymatic Activity.Med one · 2018Article
- A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis.Future medicinal chemistry · 2017Review
- Extracellular Proton Concentrations Impacts LN229 Glioblastoma Tumor Cell FateFrontiers in oncology · 2017Article
- From Krebs to clinic: glutamine metabolism to cancer therapy.Nature reviews. Cancer · 2016Review
- Article
- The Different Conformational States of Tissue Transglutaminase Have Opposing Affects on Cell Viability.The Journal of biological chemistry · 2016Article
- Compensatory Increase of Transglutaminase 2 Is Responsible for Resistance to mTOR Inhibitor Treatment.PloS one · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Most cancer cells undergo characteristic metabolic changes that are commonly referred to as the Warburg effect, with one of the hallmarks being a dramatic increase in the rate of lactic acid fermentation. This leads to the production of protons, which in turn acidifies the microenvironment surrounding tumors. Cancer cells have acquired resistance to acid toxicity, allowing them to survive and grow under these detrimental conditions. Kidney type glutaminase (GLS1), which is responsible for the conversion of glutamine to glutamate, produces ammonia as part of its catalytic activities and has been shown to modulate cellular acidity. In this study, we show that tissue, or type 2, transglutaminase (TG2), a γ-glutamyl transferase that is highly expressed in metastatic cancers and produces ammonia as a byproduct of its catalytic activity, is up-regulated by decreases in cellular pH and helps protect cells from acid-induced cell death. Since both TG2 and GLS1 can similarly function to protect cancer cells, we then proceeded to demonstrate that treatment of a variety of cancer cell types with inhibitors of each of these proteins results in synthetic lethality. The combination doses of the inhibitors induce cell death, while individual treatment with each compound shows little or no ability to kill cells. These results suggest that combination drug treatments that simultaneously target TG2 and GLS1 might provide an effective strategy for killing cancer cells.
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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.