ArticleCell death & disease2023
Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Adenosine Deaminase-Mediated Purine Dysfunction Leads to DNA Repair Inhibition and Senescence in Sporadic Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Article
- Glucose starvation induces fumarate hydratase succinylation and inhibits ferroptosis to maintain colon cancer cell proliferation.Cell death & disease · 2026Article
- TET3 promotes preeclampsia by regulating PDK4-mediated glucose metabolism reprogramming in trophoblasts.iScience · 2026Article
- Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers of early-onset colorectal cancer.Discover oncology · 2026Article
- Attenuated lamin A-prohibitin2 interaction leads to mitochondrial dysfunction in LMNA 289 A>G-mediated dilated cardiomyopathy.The Journal of biological chemistry · 2026Article
- Energy stress and adaptation strategy of tumor cells in different microenvironments: from primary tumors to distant metastases.Acta biochimica et biophysica Sinica · 2025Review
- Observational
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Inosine: biofunctions and the roles in human diseases.Frontiers in endocrinology · 2025Review
- Identification of metabolic dysregulation and biomarkers for clear cell renal cell carcinoma.Clinical and translational medicine · 2024Article
- Integrative Metabolome and Proteome Analysis of Cerebrospinal Fluid in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Multi-omic analysis identifies metabolic biomarkers for the early detection of breast cancer and therapeutic response prediction.iScience · 2024Article
- PdJournal of medicinal chemistry · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5'-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism.
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