ArticleOncogenesis2015
Diacylglycerol kinase-ζ regulates mTORC1 and lipogenic metabolism in cancer cells through SREBP-1.
Article in Oncogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed.
- The KRT15 and KRT81 complex promotes lenvatinib resistance in thyroid cancer by upregulating DGKB mediated lipid metabolism.Scientific reports · 2026Article
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- DGKζ in Glycerophospholipid Metabolism Regulates the DAG and PA Balance and Interacts With PTEN to Alleviate Brain Damage in Septic Mice With Hydrogen Inhalation: A Comparative Metabolomic and Phosphoproteomic Analysis.Brain and behavior · 2025Article
- Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases.International journal of molecular sciences · 2024Review
- Novel non-invasive molecular signatures for oral cavity cancer, by whole transcriptome and small non-coding RNA sequencing analyses: Predicted association with PI3K/AKT/mTOR pathway.Cancer medicine · 2024Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Delivering Glioblastoma a Kick-DGKα Inhibition as a Promising Therapeutic Strategy for GBM.Cancers · 2022Review
- DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2.Cell death & disease · 2022Article
- Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8Frontiers in immunology · 2022Article
- Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer.Frontiers in oncology · 2022Review
- Downregulation of Diacylglycerol kinase zeta (DGKZ) suppresses tumorigenesis and progression of cervical cancer by facilitating cell apoptosis and cell cycle arrest.Bioengineered · 2021Article
- BRCA1-BARD1 Regulates Axon Regeneration in Concert with the Gqα-DAG Signaling Network.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.International journal of molecular sciences · 2020Review
- Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases.International journal of molecular sciences · 2020Review
- Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway.Acta pharmacologica Sinica · 2019Article
- DGKζ Plays Crucial Roles in the Proliferation and Tumorigenicity of Human glioblastoma.International journal of biological sciences · 2019Article
- DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway.Frontiers in oncology · 2018Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- Diacylglycerol Kinases: Shaping Diacylglycerol and Phosphatidic Acid Gradients to Control Cell Polarity.Frontiers in cell and developmental biology · 2016Review
- Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol kinases (DGKs) transform diacylglycerol (DAG) into phosphatidic acid (PA), balancing the levels of these key metabolic and signaling lipids. We previously showed that PA derived from the DGKζ isoform promotes mammalian target of rapamycin complex 1 (mTORC1) activation. This function might be crucial for the growth and survival of cancer cells, especially for those resistant to the allosteric mTOR inhibitor rapamycin. How this positive function of DGKζ coordinates with DAG metabolism and signaling is unknown. In this study, we used a rapamycin-resistant colon cancer cell line as a model to address the role of DGKζ in tumor cells. We found that DGKζ predominated over other PA sources such as DGKα or phospholipase D to activate mTORC1, and that its activity was a component of the rapamycin-induced feedback loops. We show that the DGKζ DAG-consuming function is central to cell homeostasis, as DAG negatively regulates levels of the lipogenic transcription factor SREBP-1. Our findings suggest a model in which simultaneous regulation of DAG and PA levels by DGKζ is integrated with mTOR function to maintain tumor cell homeostasis; we provide new evidence of the crosstalk between mTOR and lipid metabolism that will be advantageous in the design of drug therapies.
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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.