ArticleOncogene2014
p73 regulates serine biosynthesis in cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Large scale integration of drug-target information reveals poly-pharmacological drug action mechanisms in tumor cell line growth inhibition assays.Oncotarget · 2014Pooled it
- Dietary serine supplementation improves growth performance and intestinal immunity and modulates gut microbiota in chronic oxidative stress-induced weaned piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Targeting amino acid metabolic pathways: a novel therapeutic strategy for hyperuricemia-associated complications.Amino acids · 2026Review
- ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.Cell death & disease · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Multi-omic characterization of consensus molecular subtype 1 (CMS1) colorectal cancer with dampened immune response improves precision medicine.Molecular oncology · 2025Article
- Phosphoglycerate dehydrogenase stabilizes protein kinase C delta type mRNA to promote hepatocellular carcinoma progression.Signal transduction and targeted therapy · 2025Article
- Metabolomic Analysis Identifies Betaine as a Key Mediator ofInternational journal of molecular sciences · 2025Article
- A novel TAp73-inhibitory compound counteracts stemness features of glioblastoma stem cells.Molecular oncology · 2025Article
- Bioinformatics analysis of PSAT1 loss identifies downstream pathways regulated in EGFR mutant NSCLC and a selective gene signature for predicting the risk of relapse.Oncology letters · 2025Article
- TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis.Cell death & disease · 2024Article
- Colorectal cancer in ulcerative colitis after liver transplantation for primary sclerosing cholangitis: a systematic review and pooled analysis of oncological outcomes.Discover oncology · 2024Review
- Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models.Molecular oncology · 2024Article
- GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Review
- Molecular profiling of a bladder cancer with very high tumour mutational burden.Cell death discovery · 2024Article
- Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma.Discover oncology · 2024Article
- Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.Cell communication and signaling : CCS · 2024Review
- Stable Isotope-Assisted Untargeted Metabolomics Identifies ALDH1A1-Driven Erythronate Accumulation in Lung Cancer Cells.Biomedicines · 2023Article
- The amino acid and carnitine concentration changes in bronchoalveolar lavage fluid from lung cancer patients.World journal of surgical oncology · 2022Article
- Structural diversity of p63 and p73 isoforms.Cell death and differentiation · 2022Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Activation of serine biosynthesis supports growth and proliferation of cancer cells. Human cancers often exhibit overexpression of phosphoglycerate dehydrogenase (PHGDH), the metabolic enzyme that catalyses the reaction that diverts serine biosynthesis from the glycolytic pathway. By refueling serine biosynthetic pathways, cancer cells sustain their metabolic requirements, promoting macromolecule synthesis, anaplerotic flux and ATP. Serine biosynthesis intersects glutaminolysis and together with this pathway provides substrates for production of antioxidant GSH. In human lung adenocarcinomas we identified a correlation between serine biosynthetic pathway and p73 expression. Metabolic profiling of human cancer cell line revealed that TAp73 activates serine biosynthesis, resulting in increased intracellular levels of serine and glycine, associated to accumulation of glutamate, tricarboxylic acid (TCA) anaplerotic intermediates and GSH. However, at molecular level p73 does not directly regulate serine metabolic enzymes, but transcriptionally controls a key enzyme of glutaminolysis, glutaminase-2 (GLS-2). p73, through GLS-2, favors conversion of glutamine in glutamate, which in turn drives the serine biosynthetic pathway. Serine and glutamate can be then employed for GSH synthesis, thus the p73-dependent metabolic switch enables potential response against oxidative stress. In knockdown experiment, indeed, TAp73 depletion completely abrogates cancer cell proliferation capacity in serine/glycine-deprivation, supporting the role of p73 to help cancer cells under metabolic stress. These findings implicate p73 in regulation of cancer metabolism and suggest that TAp73 influences glutamine and serine metabolism, affecting GSH synthesis and determining cancer pathogenesis.
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