The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers
Open accessAbstract
The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.
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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
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922
p53 Regulates Mitochondrial Respiration
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M. (2006) · Science · doi:10.1126/science.1126863 · Cited by 1,650
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635
Akt Stimulates Aerobic Glycolysis in Cancer Cells
Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2904 · Cited by 1,454
HIF-1 and tumor progression: pathophysiology and therapeutics
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Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885
Cited by
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505
Tumour acidosis: from the passenger to the driver's seat
Corbet, C., & Feron, O. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.77 · Cited by 988
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review)
ZHENG, J. (2012) · Oncology Letters · doi:10.3892/ol.2012.928 · Cited by 963
Drug Resistance and Cellular Adaptation to Tumor Acidic pH Microenvironment
Wojtkowiak, J. W., Verduzco, D., Schramm, K. J., & Gillies, R. J. (2011) · Molecular Pharmaceutics · doi:10.1021/mp200292c · Cited by 566
Acidic tumor microenvironment and pH-sensing G protein-coupled receptors
Justus, C. R., Dong, L., & Yang, L. V. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00354 · Cited by 374
Metadata
- Authors
- Chen, J. L.-Y., Lucas, J. E., Schroeder, T., Mori, S., Wu, J., Nevins, J., Dewhirst, M., West, M., & Chi, J.-T.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-12-05
- Volume
- 4
- Issue
- 12
- Pages
- e1000293
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- OpenAlex
- W1972220057
- Cited by
- 213
- References
- 11
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- gold
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- Chen, J. L.-Y., Lucas, J. E., Schroeder, T., Mori, S., Wu, J., Nevins, J., Dewhirst, M., West, M., & Chi, J.-T. (2008). The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1000293
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