ArticleJournal of experimental & clinical cancer research : CR2021
SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Intelligent plant exosomes synergize miRNAs and cisplatin for spatiotemporally precise multimodal treatment for TNBC with high safety.Bioactive materials · 2026Article
- Targeting SLC6A8 suppresses tumor growth and enhances ferroptosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2026Article
- Rougan Tongluo Decoction Initiates Neuroprotection Against Cerebral Ischemia by Activating the Endogenous SLC6A8-Creatine-EARS2 Mitochondrial Pathway.Mediators of inflammation · 2026Article
- The Role of CAF-derived Vitronectin in Promoting Colorectal Cancer Progression and Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Empowering hypoxia to convert cold tumors into hot tumors for breast cancer immunotherapy.Cell death discovery · 2025Review
- Gene Expression in Muscle-Invasive and Non-Muscle-Invasive Bladder Cancer Cells Exposed to Hypoxia.Cancers · 2025Article
- SIMVI disentangles intrinsic and spatial-induced cellular states in spatial omics data.Nature communications · 2025Article
- Assessing Creatine-Related Gene Expression in Kidney Disease: Can Available Data Give Insights into an Old Discussion?Nutrients · 2025Review
- Review of electrophysiological models to study membrane potential changes in breast cancer cell transformation and tumor progression.Frontiers in physiology · 2025Review
- Targeting Creatine and Creatine Kinase in Cancer: Exploring Potential Therapeutic Strategies.Current drug targets · 2025Review
- It Is Not Just About Storing Energy: The Multifaceted Role of Creatine Metabolism on Cancer Biology and Immunology.International journal of molecular sciences · 2024Review
- SIMVI reveals intrinsic and spatial-induced states in spatial omics data.bioRxiv : the preprint server for biology · 2024Article
- Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway.Acta pharmaceutica Sinica. B · 2024Article
- A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.Scientific reports · 2024Article
- Structural Studies of the Taurine Transporter: A Potential Biological Target from the GABA Transporter Subfamily in Cancer Therapy.International journal of molecular sciences · 2024Article
- Intestinal Epithelial Creatine Transporter SLC6A8 Dysregulation in Inflammation and in Response to Adherent InvasiveInternational journal of molecular sciences · 2024Article
- Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth.Cell metabolism · 2024Article
- Transcriptomics integrated with metabolomics reveals partial molecular mechanisms of nutritional risk and neurodevelopment in children with congenital heart disease.Frontiers in cardiovascular medicine · 2024Article
- RGCC-mediated PLK1 activity drives breast cancer lung metastasis by phosphorylating AMPKα2 to activate oxidative phosphorylation and fatty acid oxidation.Journal of experimental & clinical cancer research : CR · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia.
methodsRNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O
resultsSLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3.
conclusionsOur study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.
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