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Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival

Author

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  • Edoardo Gaude

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre)

  • Christian Frezza

    (MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre)

Abstract

Cancer cells undergo a multifaceted rewiring of cellular metabolism to support their biosynthetic needs. Although the major determinants of this metabolic transformation have been elucidated, their broad biological implications and clinical relevance are unclear. Here we systematically analyse the expression of metabolic genes across 20 different cancer types and investigate their impact on clinical outcome. We find that cancers undergo a tissue-specific metabolic rewiring, which converges towards a common metabolic landscape. Of note, downregulation of mitochondrial genes is associated with the worst clinical outcome across all cancer types and correlates with the expression of epithelial-to-mesenchymal transition gene signature, a feature of invasive and metastatic cancers. Consistently, suppression of mitochondrial genes is identified as a key metabolic signature of metastatic melanoma and renal cancer, and metastatic cell lines. This comprehensive analysis reveals unexpected facets of cancer metabolism, with important implications for cancer patients’ stratification, prognosis and therapy.

Suggested Citation

  • Edoardo Gaude & Christian Frezza, 2016. "Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival," Nature Communications, Nature, vol. 7(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13041
    DOI: 10.1038/ncomms13041
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    Cited by:

    1. Giovanni Codacci-Pisanelli, 2017. "Epigenetic Targets in the Treatment of cancer," Novel Approaches in Drug Designing & Development, Juniper Publishers Inc., vol. 1(4), pages 56-57, June.
    2. Tea Pemovska & Johannes W. Bigenzahn & Ismet Srndic & Alexander Lercher & Andreas Bergthaler & Adrián César-Razquin & Felix Kartnig & Christoph Kornauth & Peter Valent & Philipp B. Staber & Giulio Sup, 2021. "Metabolic drug survey highlights cancer cell dependencies and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    3. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Marco Sciacovelli & Aurelien Dugourd & Lorea Valcarcel Jimenez & Ming Yang & Efterpi Nikitopoulou & Ana S. H. Costa & Laura Tronci & Veronica Caraffini & Paulo Rodrigues & Christina Schmidt & Dylan Ge, 2022. "Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Jia-Cheng Lu & Lei-Lei Wu & Yi-Ning Sun & Xiao-Yong Huang & Chao Gao & Xiao-Jun Guo & Hai-Ying Zeng & Xu-Dong Qu & Yi Chen & Dong Wu & Yan-Zi Pei & Xian-Long Meng & Yi-Min Zheng & Chen Liang & Peng-Fe, 2024. "Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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