ArticleEMBO reports2020
The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Machine learning-optimized metabolic biomarker panel for precision screening of early-stage pancreatic cancer in new-onset diabetes.Frontiers in endocrinology · 2025Article
- How mitochondrial dynamics imbalance affects the progression of breast cancer:a mini review.Medical oncology (Northwood, London, England) · 2024Review
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
- Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment.Advances in nutrition (Bethesda, Md.) · 2023Review
- Selective ablation of 3' RNA ends and processive RTs facilitate direct cDNA sequencing of full-length host cell and viral transcripts.Nucleic acids research · 2022Article
- The role of serine metabolism in lung cancer: From oncogenesis to tumor treatment.Frontiers in genetics · 2022Review
- The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism.EMBO reports · 2020Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
IκB kinase ε (IKKε) is a key molecule at the crossroads of inflammation and cancer. Known to regulate cytokine secretion via NFκB and IRF3, the kinase is also a breast cancer oncogene, overexpressed in a variety of tumours. However, to what extent IKKε remodels cellular metabolism is currently unknown. Here, we used metabolic tracer analysis to show that IKKε orchestrates a complex metabolic reprogramming that affects mitochondrial metabolism and consequently serine biosynthesis independently of its canonical signalling role. We found that IKKε upregulates the serine biosynthesis pathway (SBP) indirectly, by limiting glucose-derived pyruvate utilisation in the TCA cycle, inhibiting oxidative phosphorylation. Inhibition of mitochondrial function induces activating transcription factor 4 (ATF4), which in turn drives upregulation of the expression of SBP genes. Importantly, pharmacological reversal of the IKKε-induced metabolic phenotype reduces proliferation of breast cancer cells. Finally, we show that in a highly proliferative set of ER negative, basal breast tumours, IKKε and PSAT1 are both overexpressed, corroborating the link between IKKε and the SBP in the clinical context.
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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.