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Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival
Open accessAbstract
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.
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863
Huber, W., von Heydebreck, A., Sültmann, H., Poustka, A., & Vingron, M. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.suppl_1.s96 · Cited by 2,440
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108 · cited 1×
“Together with these findings, our results showed diminished expression of TCA cycle enzymes in cancer, and Succinate Dehydrogenase D ( SDHD ) ranked among the most frequently downregulated mitochondrial genes, in line with its role as mitochondrial tumour suppressor 17 .”
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791
Proteogenomic characterization of human colon and rectal cancer
CPTAC, T. N., Zhang, B., Wang, J., Wang, X., Zhu, J., Liu, Q., Shi, Z., Chambers, M. C., Zimmerman, L. J., Shaddox, K. F., et al. (2014) · Nature · doi:10.1038/nature13438 · Cited by 1,462
LeBleu, V. S., O’Connell, J. T., Gonzalez Herrera, K. N., Wikman, H., Pantel, K., Haigis, M. C., de Carvalho, F. M., Damascena, A., Domingos Chinen, L. T., Rocha, R. M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3039 · Cited by 1,404
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403
Global reconstruction of the human metabolic network based on genomic and bibliomic data
Duarte, N. C., Becker, S. A., Jamshidi, N., Thiele, I., Mo, M. L., Vo, T. D., Srivas, R., & Palsson, B. Ø. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610772104 · Cited by 1,374
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328
Epithelial–mesenchymal plasticity in carcinoma metastasis
Tsai, J. H., & Yang, J. (2013) · Genes & Development · doi:10.1101/gad.225334.113 · Cited by 1,136
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma
Hakimi, A. A., Reznik, E., Lee, C.-H., Creighton, C. J., Brannon, A. R., Luna, A., Aksoy, B. A., Liu, E. M., Shen, R., Lee, W., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.004 · Cited by 798
Tan, A. S., Baty, J. W., Dong, L.-F., Bezawork-Geleta, A., Endaya, B., Goodwin, J., Bajzikova, M., Kovarova, J., Peterka, M., Yan, B., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.003 · Cited by 785
Väremo, L., Nielsen, J., & Nookaew, I. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt111 · Cited by 697
�ber den Stoffwechsel der Carcinomzelle
Warburg, O. (1924) · Die Naturwissenschaften · doi:10.1007/bf01504608 · Cited by 631
A Mitochondrial Switch Promotes Tumor Metastasis
Porporato, P. E., Payen, V. L., Pérez-Escuredo, J., De Saedeleer, C. J., Danhier, P., Copetti, T., Dhup, S., Tardy, M., Vazeille, T., Bouzin, C., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.043 · Cited by 571
Mitochondrial DNA copy number variation across human cancers
Reznik, E., Miller, M. L., Şenbabaoğlu, Y., Riaz, N., Sarungbam, J., Tickoo, S. K., Al-Ahmadie, H. A., Lee, W., Seshan, V. E., Hakimi, A. A., et al. (2016) · eLife · doi:10.7554/elife.10769 · Cited by 530
MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis
Terunuma, A., Putluri, N., Mishra, P., Mathé, E. A., Dorsey, T. H., Yi, M., Wallace, T. A., Issaq, H. J., Zhou, M., Killian, J. K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71180 · Cited by 428
Heterogeneity of tumor-induced gene expression changes in the human metabolic network
Hu, J., Locasale, J. W., Bielas, J. H., O'Sullivan, J., Sheahan, K., Cantley, L. C., Heiden, M. G. V., & Vitkup, D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2530 · Cited by 407
Cowley, G. S., Weir, B. A., Vazquez, F., Tamayo, P., Scott, J. A., Rusin, S., East-Seletsky, A., Ali, L. D., Gerath, W. F., Pantel, S. E., et al. (2014) · Scientific Data · doi:10.1038/sdata.2014.35 · Cited by 387
Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
Fendt, S.-M., Bell, E. L., Keibler, M. A., Olenchock, B. A., Mayers, J. R., Wasylenko, T. M., Vokes, N. I., Guarente, L., Heiden, M. G. V., & Stephanopoulos, G. (2013) · Nature Communications · doi:10.1038/ncomms3236 · Cited by 364 · cited 1×
“For instance, reductive citrate has been shown to support lipid synthesis under hypoxia 22 , in the presence of TCA cycle truncation 23 , or in the presence of respiratory chain inhibitors 24 .”
Cho, V., Mei, Y., Sanny, A., Chan, S., Enders, A., Bertram, E. M., Tan, A., Goodnow, C. C., & Andrews, T. D. (2014) · Genome Biology · doi:10.1186/gb-2014-15-1-r26 · Cited by 339
Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer
Vanharanta, S., Shu, W., Brenet, F., Hakimi, A. A., Heguy, A., Viale, A., Reuter, V. E., Hsieh, J. J.-D., Scandura, J. M., & Massagué, J. (2013) · Nature Medicine · doi:10.1038/nm.3029 · Cited by 215
The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
Torrano, V., Valcarcel-Jimenez, L., Cortazar, A. R., Liu, X., Urosevic, J., Castillo-Martin, M., Fernández-Ruiz, S., Morciano, G., Caro-Maldonado, A., Guiu, M., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3357 · Cited by 212
(1994) · PubMed · Cited by 109
Bartesaghi, S., Graziano, V., Galavotti, S., Henriquez, N. V., Betts, J., Saxena, J., Minieri, V., Deli, A., Karlsson, A., Martins, L. M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1413165112 · Cited by 78
Gross, A. M., Kreisberg, J. F., & Ideker, T. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142618 · Cited by 44
Extensive Decoupling of Metabolic Genes in Cancer
Reznik, E., & Sander, C. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004176 · Cited by 40
Copy Number Alterations in Enzyme-Coding and Cancer-Causing Genes Reprogram Tumor Metabolism
Sharma, A. K., Eils, R., & König, R. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2350 · Cited by 19
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The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
Metabolites and the Tumour Microenvironment: From Cellular Mechanisms to Systemic Metabolism
Elia, I., & Haigis, M. C. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00317-z · Cited by 651
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Metadata
- Authors
- Gaude, E., & Frezza, C.
- Venue
- Nature Communications
- Published
- 2016-10-10
- Volume
- 7
- Issue
- 1
- Pages
- 13041-13041
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2528569964
- Cited by
- 375
- References
- 32
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- gold
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