ArticleBritish journal of cancer2023
Transcription factor NKX2-1 drives serine and glycine synthesis addiction in cancer.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- NKX2-1 regulates cell survival, maturation, and DNAdamage responses as a cofactor of RUNX1 in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.Cell death & disease · 2026Article
- 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
- Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms.Pharmacology research & perspectives · 2025Article
- NKX2-1 Restricts the Growth and Metastasis of Lung Squamous Cell Carcinoma Through Transcriptive Suppression of AKR1B10.Journal of biochemical and molecular toxicology · 2025Article
- T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments.Leukemia · 2025Review
- TET2 gene mutation status associated with poor prognosis of transition zone prostate cancer: a retrospective cohort study based on whole exome sequencing and machine learning models.Frontiers in endocrinology · 2025Article
- Understanding serine and glycine metabolism in cancer: a path towards precision medicine to improve patient's outcomes.Discover oncology · 2024Review
- Sertraline/chloroquine combination therapy to target hypoxic and immunosuppressive serine/glycine synthesis-dependent glioblastomas.Oncogenesis · 2024Article
- TMO-Net: an explainable pretrained multi-omics model for multi-task learning in oncology.Genome biology · 2024Article
- Association of polymorphism in the promotor area of the caprine BMPR1B gene with litter size and body measurement traits in Damani goats.Tropical animal health and production · 2024Article
- Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells.Cancer & metabolism · 2024Article
- SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma.PloS one · 2024Article
- PSMA-targeted radiotheranostics in modern nuclear medicine: then, now, and what of the future?Theranostics · 2024Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOne-third of cancers activate endogenous synthesis of serine/glycine, and can become addicted to this pathway to sustain proliferation and survival. Mechanisms driving this metabolic rewiring remain largely unknown.
methodsNKX2-1 overexpressing and NKX2-1 knockdown/knockout T-cell leukaemia and lung cancer cell line models were established to study metabolic rewiring using ChIP-qPCR, immunoblotting, mass spectrometry, and proliferation and invasion assays. Findings and therapeutic relevance were validated in mouse models and confirmed in patient datasets.
resultsExploring T-cell leukaemia, lung cancer and neuroendocrine prostate cancer patient datasets highlighted the transcription factor NKX2-1 as putative driver of serine/glycine metabolism. We demonstrate that transcription factor NKX2-1 binds and transcriptionally upregulates serine/glycine synthesis enzyme genes, enabling NKX2-1 expressing cells to proliferate and invade in serine/glycine-depleted conditions. NKX2-1 driven serine/glycine synthesis generates nucleotides and redox molecules, and is associated with an altered cellular lipidome and methylome. Accordingly, NKX2-1 tumour-bearing mice display enhanced tumour aggressiveness associated with systemic metabolic rewiring. Therapeutically, NKX2-1-expressing cancer cells are more sensitive to serine/glycine conversion inhibition by repurposed anti-depressant sertraline, and to etoposide chemotherapy.
conclusionCollectively, we identify NKX2-1 as a novel transcriptional regulator of serine/glycine synthesis addiction across cancers, revealing a therapeutic vulnerability of NKX2-1-driven cancers. Transcription factor NKX2-1 fuels cancer cell proliferation and survival by hyperactivating serine/glycine synthesis, highlighting this pathway as a novel therapeutic target in NKX2-1-positive cancers.
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