ArticleNature metabolism2024
The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Targeting PSAT1 in diabetic kidney disease: a ferroptosis-driven strategy for precision therapy.Molecular and cellular biochemistry · 2026Article
- GLYATL1 is associated with metabolic and epigenetic changes and with endocrine resistance in luminal breast cancer.Clinical epigenetics · 2026Article
- Cancer-immunity cycle-based molecular subtypes in breast cancer predict the response to immune checkpoint inhibitors.Cancer biology & medicine · 2026Article
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- Microbiota-driven metabolic-immune crosstalk in breast cancer.Frontiers in pharmacology · 2026Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Comparative analysis of the effects of PSPH and PHGDH inhibitors on tumor cell proliferation.Investigational new drugs · 2025Article
- Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Review
- De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma.Cancer research · 2025Article
- PSAT1 regulates hair follicle growth and stem cell behavior in cashmere goats.BMC veterinary research · 2025Article
- Recent progress in serine metabolism reprogramming in tumors and strategies for serine deprivation.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Cultured cancer cells frequently rely on the consumption of glutamine and its subsequent hydrolysis by glutaminase (GLS). However, this metabolic addiction can be lost in the tumour microenvironment, rendering GLS inhibitors ineffective in the clinic. Here we show that glutamine-addicted breast cancer cells adapt to chronic glutamine starvation, or GLS inhibition, via AMPK-mediated upregulation of the serine synthesis pathway (SSP). In this context, the key product of the SSP is not serine, but α-ketoglutarate (α-KG). Mechanistically, we find that phosphoserine aminotransferase 1 (PSAT1) has a unique capacity for sustained α-KG production when glutamate is depleted. Breast cancer cells with resistance to glutamine starvation or GLS inhibition are highly dependent on SSP-supplied α-KG. Accordingly, inhibition of the SSP prevents adaptation to glutamine blockade, resulting in a potent drug synergism that suppresses breast tumour growth. These findings highlight how metabolic redundancy can be context dependent, with the catalytic properties of different metabolic enzymes that act on the same substrate determining which pathways can support tumour growth in a particular nutrient environment. This, in turn, has practical consequences for therapies targeting cancer metabolism.
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