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Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

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  • Kıvanç Birsoy

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center
    Massachusetts Institute of Technology
    Broad Institute of Harvard and MIT, Seven Cambridge Center
    The David H. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue)

  • Richard Possemato

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center
    Massachusetts Institute of Technology
    Broad Institute of Harvard and MIT, Seven Cambridge Center
    The David H. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue)

  • Franziska K. Lorbeer

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center)

  • Erol C. Bayraktar

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center)

  • Prathapan Thiru

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center)

  • Burcu Yucel

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center)

  • Tim Wang

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center
    Massachusetts Institute of Technology
    Broad Institute of Harvard and MIT, Seven Cambridge Center
    The David H. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue)

  • Walter W. Chen

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center
    Massachusetts Institute of Technology
    Broad Institute of Harvard and MIT, Seven Cambridge Center
    The David H. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue)

  • Clary B. Clish

    (Broad Institute of Harvard and MIT, Seven Cambridge Center)

  • David M. Sabatini

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center
    Massachusetts Institute of Technology
    Broad Institute of Harvard and MIT, Seven Cambridge Center
    The David H. Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue)

Abstract

New apparatus is used to maintain proliferating cancer cells in low-glucose conditions, demonstrating that mitochondrial oxidative phosphorylation (OXPHOS) is essential for optimal proliferation in these conditions; the most sensitive cell lines are defective in OXPHOS upregulation and may therefore be sensitive to current antidiabetic drugs that inhibit OXPHOS.

Suggested Citation

  • Kıvanç Birsoy & Richard Possemato & Franziska K. Lorbeer & Erol C. Bayraktar & Prathapan Thiru & Burcu Yucel & Tim Wang & Walter W. Chen & Clary B. Clish & David M. Sabatini, 2014. "Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides," Nature, Nature, vol. 508(7494), pages 108-112, April.
    • Handle: RePEc:nat:nature:v:508:y:2014:i:7494:d:10.1038_nature13110
    DOI: 10.1038/nature13110
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    Cited by:

    1. Xianbing Zhu & Zheng Fu & Shary Y. Chen & Dionzie Ong & Giulio Aceto & Rebecca Ho & Jutta Steinberger & Anie Monast & Virginie Pilon & Eunice Li & Monica Ta & Kyle Ching & Bianca N. Adams & Gian L. Ne, 2023. "Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Shuaifeng Li & Shixun Han & Qi Zhang & Yibing Zhu & Haitao Zhang & Junli Wang & Yang Zhao & Jianhui Zhao & Lin Su & Li Li & Dawang Zhou & Cunqi Ye & Xin-Hua Feng & Tingbo Liang & Bin Zhao, 2022. "FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Xin Yuan & Yanran Ma & Ruitian Gao & Shuya Cui & Yifan Wang & Botao Fa & Shiyang Ma & Ting Wei & Shuangge Ma & Zhangsheng Yu, 2024. "HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Marc Hennequart & Christiaan F. Labuschagne & Mylène Tajan & Steven E. Pilley & Eric C. Cheung & Nathalie M. Legrave & Paul C. Driscoll & Karen H. Vousden, 2021. "The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Yuanli Zhen & Kai Liu & Lei Shi & Simran Shah & Qin Xu & Haley Ellis & Eranga R. Balasooriya & Johannes Kreuzer & Robert Morris & Albert S. Baldwin & Dejan Juric & Wilhelm Haas & Nabeel Bardeesy, 2024. "FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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