ArticleProceedings of the National Academy of Sciences of the United States of America2021
Reprogrammed transsulfuration promotes basal-like breast tumor progression via realigning cellular cysteine persulfidation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.Nature communications · 2026Article
- Multifaceted roles for persulfide species in redox chemical biology.Nature chemical biology · 2026Review
- Aspartate treatment ameliorates metabolic dysfunction-associated fatty liver disease through upregulation of CBS and suppression of ferroptosis.The Journal of biological chemistry · 2026Article
- Next-Generation Redox Mediators: Itaconate, Nitro-Fatty Acids, Reactive Sulfur Species and Succinate as Emerging Switches in Predictive Redox Medicine.Antioxidants (Basel, Switzerland) · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Distinct control of T cell proliferation and effector function by partitioning of intracellular sulfur from cysteine.bioRxiv : the preprint server for biology · 2026Article
- Esterase-Responsive Mitochondria-Targeted Hydropersulfide Donors Mitigate Doxorubicin Cardiotoxicity While Preserving Anticancer Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Gasotransmitters bridging tumor biology and immunity: from pathophysiological insights to therapeutic potential.Frontiers in immunology · 2026Review
- Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Transsulfuration metabolism is essential for ferroptosis resistance in quiescent endothelial cells.Cell death & disease · 2025Article
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Power and poison: The intersections of HThe Journal of biological chemistry · 2025Review
- Metabolic Regulation of Ferroptosis in Breast Cancer.International journal of molecular sciences · 2025Review
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Targeting the Exonic CircularResearch (Washington, D.C.) · 2025Article
- Emerging roles of hydrogen sulfide-metabolizing enzymes in cancer.Redox report : communications in free radical research · 2024Review
- Neurobehavioral dysfunction in a mouse model of Down syndrome: upregulation of cystathionine β-synthase, HGeroScience · 2024Article
- Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.Molecules (Basel, Switzerland) · 2024Review
- Role of hydrogen sulfide in health and disease.MedComm · 2024Review
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione β-synthetase (CBS). CBS silencing (shCBS) made BLBC cells less invasive, proliferate slower, more vulnerable to oxidative stress and cystine (CySSCy) deprivation, prone to ferroptosis, and less responsive to HIF1-α activation under hypoxia. shCBS xenograft tumors grew slower than controls and exhibited impaired angiogenesis and larger necrotic areas. Sulfur metabolite profiling suggested that realigned sulfide/persulfide-inducing functions of CBS are important in BLBC tumor progression. Supporting this, the exclusion of serine, a substrate of CBS for producing Cys but not for producing sulfide/persulfide, did not exacerbate CySSCy deprivation-induced ferroptosis in shCBS BLBC cells. Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. Hence, the persulfide-producing pathways are major targetable determinants of BLBC pathology that could be therapeutically exploited.
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