ArticleCell reports2021
ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restriction.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- Rewiring of de novo serine synthesis supports tumorigenesis under deficiency of TET2.British journal of cancer · 2026Article
- Review
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Article
- L-serine at the crossroads of microbiota, intestinal health, and disorders.Communications biology · 2026Review
- PSAT1 Promotes NSCLC Progression via the De Novo Serine Synthesis Pathway and Represents a Therapeutic Vulnerability.Cancer medicine · 2026Article
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Large-scale single-cell analysis and in silico perturbation reveal dynamic evolution of HCC: from initiation to therapeutic targeting.NPJ precision oncology · 2026Article
- MiR-181a-5p/CDK6 axis attenuates cell proliferation, migration and glycolytic reprogramming in oral squamous cell carcinoma.Cancer cell international · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Targeting serine synthesis pathway to reverse paclitaxel resistance in NSCLC with combination of paclitaxel and anlotinib.Journal of experimental & clinical cancer research : CR · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Integrative Bioinformatics Reveals Novel Molecular Mechanisms and Therapeutic Targets in Acute Myeloid Leukaemia.Journal of cellular and molecular medicine · 2026Article
- Metabolic remodeling and immune evasion in glioblastoma: a focus on serine and lipid networks.Frontiers in oncology · 2026Review
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma.Genes & diseases · 2025Article
- NRF2-SOX4 complex regulates PSPH in hepatocellular carcinoma and modulates M2 macrophage differentiation.Cancer gene therapy · 2025Article
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The serine synthesis pathway (SSP) involving metabolic enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) drives intracellular serine biosynthesis and is indispensable for cancer cells to grow in serine-limiting environments. However, how SSP is regulated is not well understood. Here, we report that activating transcription factor 3 (ATF3) is crucial for transcriptional activation of SSP upon serine deprivation. ATF3 is rapidly induced by serine deprivation via a mechanism dependent on ATF4, which in turn binds to ATF4 and increases the stability of this master regulator of SSP. ATF3 also binds to the enhancers/promoters of PHGDH, PSAT1, and PSPH and recruits p300 to promote expression of these SSP genes. As a result, loss of ATF3 expression impairs serine biosynthesis and the growth of cancer cells in the serine-deprived medium or in mice fed with a serine/glycine-free diet. Interestingly, ATF3 expression positively correlates with PHGDH expression in a subset of TCGA cancer samples.
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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.