{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:33:43Z","timestamp":1790681623602,"version":"4.1.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81001419"],"award-info":[{"award-number":["81001419"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nattional Natural Science Foundation of China","award":["81273478"],"award-info":[{"award-number":["81273478"]}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2012ZX09301003-001-010"],"award-info":[{"award-number":["2012ZX09301003-001-010"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Extracellular acidosis is considered as a hallmark of most human tumors, which plays an important role in promoting tumor malignant and aggressive phenotype in tumorigenesis. Acidosis and lactic acidosis can induce different responses in tumors. Previous studies have associated the response to lactic acidosis of tumors with good survival outcomes. In this study, we investigated the metabolomic changes in triple negative and luminal subtype breast cancer cell lines in response to acidosis and lactic acidosis. Our results showed that acidosis results in the reduction of cell viability and glycolysis in breast cancer cells, which is reversely correlated with the malignancy of cell lines. Under lactic acidosis, this reduction is reversed slightly. Untargeted metabolomic profiling revealed that glutaminolysis and fatty acid synthesis in cancer cells under acidosis are increased, while TCA cycle and glycolysis are decreased. Under lactic acidosis, the pentose phosphate pathway and acetate release are increased in MDA-MB-231 cells. The current results uncovered the different metabolic responses of breast cancer cells to acidosis and lactic acidosis, demonstrating the power of combined untargeted and stable isotope assisted metabolomics in comprehensive metabolomic analysis.<\/jats:p>","DOI":"10.1038\/s41598-020-78955-2","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T11:04:54Z","timestamp":1608030294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Differential metabolic responses in breast cancer cell lines to acidosis and lactic acidosis revealed by stable isotope assisted metabolomics"],"prefix":"10.1038","volume":"10","author":[{"given":"Jiayue","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangting","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"78955_CR1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1002\/jcp.24221","volume":"228","author":"A Hulikova","year":"2013","unstructured":"Hulikova, A., Harris, A. L., Vaughan-Jones, R. D. & Swietach, P. Regulation of intracellular pH in cancer cell lines under normoxia and hypoxia. J. Cell Physiol. 228, 743\u2013752 (2013).","journal-title":"J. Cell Physiol."},{"key":"78955_CR2","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1038\/sj.emboj.7600196","volume":"23","author":"M Koshiji","year":"2004","unstructured":"Koshiji, M. et al. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J. 23, 1949\u20131956 (2004).","journal-title":"EMBO J."},{"key":"78955_CR3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.ccr.2007.02.006","volume":"11","author":"JD Gordan","year":"2007","unstructured":"Gordan, J. D., Bertout, J. A., Hu, C. J., Diehl, J. A. & Simon, M. C. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 11, 335\u2013347 (2007).","journal-title":"Cancer Cell"},{"key":"78955_CR4","doi-asserted-by":"publisher","first-page":"11960","DOI":"10.1038\/ncomms11960","volume":"7","author":"X Gao","year":"2016","unstructured":"Gao, X. et al. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat. Commun. 7, 11960 (2016).","journal-title":"Nat. Commun."},{"key":"78955_CR5","doi-asserted-by":"publisher","first-page":"a026583","DOI":"10.1101\/cshperspect.a026583","volume":"6","author":"Y Yuan","year":"2016","unstructured":"Yuan, Y. Spatial heterogeneity in the tumor microenvironment. Cold Spring Harb. Perspect Med.. 6, a026583 (2016).","journal-title":"Cold Spring Harb. Perspect Med.."},{"key":"78955_CR6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.gde.2010.10.006","volume":"21","author":"MC Brahimi-Horn","year":"2011","unstructured":"Brahimi-Horn, M. C., Bellot, G. & Pouyss\u00e9gur, J. Hypoxia and energetic tumour metabolism. Curr. Opin. Genet. Dev. 21, 2 (2011).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"78955_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s11306-017-1308-6","volume":"14","author":"J Yang","year":"2018","unstructured":"Yang, J. et al. Untargeted and stable isotope-assisted metabolomic analysis of MDA-MB-231 cells under hypoxia. Metabolomics 14, 14 (2018).","journal-title":"Metabolomics"},{"key":"78955_CR8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.bbamcr.2016.03.013","volume":"1863","author":"J P\u00e9rez-Escuredo","year":"2016","unstructured":"P\u00e9rez-Escuredo, J. et al. Monocarboxylate transporters in the brain and in cancer. Biochem. Biophys. Acta. 1863, 17 (2016).","journal-title":"Biochem. Biophys. Acta."},{"key":"78955_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bbamcr.2016.02.018","volume":"1863","author":"L Counillon","year":"2016","unstructured":"Counillon, L., Bouret, Y., Marchiq, I. & Pouyss\u00e9gur, J. Na+\/H+ antiporter (NHE1) and lactate\/H+ symporters (MCTs) in pH homeostasis and cancer metabolism. Biochem. Biophys. Acta. 1863, 16 (2016).","journal-title":"Biochem. Biophys. Acta."},{"key":"78955_CR10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12943-016-0502-x","volume":"15","author":"PA Anne","year":"2016","unstructured":"Anne, P. A. et al. Roles of acid-extruding ion transporters in regulation of breast cancer cell growth in a 3-dimensional microenvironment. Mol. Cancer 15, 18 (2016).","journal-title":"Mol. Cancer"},{"key":"78955_CR11","first-page":"453","volume":"39","author":"K Goetze","year":"2011","unstructured":"Goetze, K., Walenta, S., Ksiazkiewicz, M., Kunz-Schughart, L. A. & Mueller-Klieser, W. Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int. J. Oncol. 39, 453\u2013463 (2011).","journal-title":"Int. J. Oncol."},{"key":"78955_CR12","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.molcel.2012.10.025","volume":"49","author":"MA McBrian","year":"2013","unstructured":"McBrian, M. A. et al. Histone acetylation regulates intracellular pH. Mol. Cell 49, 310\u2013321 (2013).","journal-title":"Mol. Cell"},{"key":"78955_CR13","first-page":"2","volume":"15","author":"JV Panagiotis","year":"2015","unstructured":"Panagiotis, J. V., Katerina, G. O., Eugene, G. & George, A. Elevated lactic acid is a negative prognostic factor in metastatic lung cancer. Cancer Biomark. 15, 2 (2015).","journal-title":"Cancer Biomark."},{"key":"78955_CR14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/nrc2255","volume":"8","author":"RA Gatenby","year":"2008","unstructured":"Gatenby, R. A. & Gillies, R. J. A microenvironmental model of carcinogenesis. Nat. Rev. Cancer 8, 2 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"78955_CR15","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nrc3110","volume":"11","author":"BA Webb","year":"2011","unstructured":"Webb, B. A., Chimenti, M., Jacobson, M. P. & Barber, D. L. Dysregulated pH: A perfect storm for cancer progression. Nat. Rev. Cancer 11, 671\u2013677 (2011).","journal-title":"Nat. Rev. Cancer"},{"key":"78955_CR16","first-page":"1194","volume":"56","author":"LE Gerweck","year":"1996","unstructured":"Gerweck, L. E. & Seetharaman, K. Cellular pH gradient in tumor versus normal tissue: Potential exploitation for the treatment of cancer. Cancer Res. 56, 1194\u20131198 (1996).","journal-title":"Cancer Res."},{"key":"78955_CR17","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nm0297-177","volume":"3","author":"G Helmlinger","year":"1997","unstructured":"Helmlinger, G., Yuan, F., Dellian, M. & Jain, R. K. Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation. Nat. Med. 3, 177\u2013182 (1997).","journal-title":"Nat. Med."},{"key":"78955_CR18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S1357-4310(99)01615-9","volume":"6","author":"M Stubbs","year":"2000","unstructured":"Stubbs, M., McSheehy, P. M., Griffiths, J. R. & Bashford, C. L. Causes and consequences of tumour acidity and implications for treatment. Mol. Med. Today 6, 15\u201319 (2000).","journal-title":"Mol. Med. Today"},{"key":"78955_CR19","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1158\/0008-5472.CAN-07-5575","volume":"69","author":"IF Robey","year":"2009","unstructured":"Robey, I. F. et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 69, 2260\u20132268 (2009).","journal-title":"Cancer Res."},{"key":"78955_CR20","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.cell.2017.09.019","volume":"171","author":"B Faubert","year":"2017","unstructured":"Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358\u2013371 (2017).","journal-title":"Cell"},{"key":"78955_CR21","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/2049-3002-1-23","volume":"1","author":"G Lamonte","year":"2013","unstructured":"Lamonte, G. et al. Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress. Cancer Metab 1, 23 (2013).","journal-title":"Cancer Metab"},{"key":"78955_CR22","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/j.cell.2008.08.021","volume":"134","author":"PP Hsu","year":"2008","unstructured":"Hsu, P. P. & Sabatini, D. M. Cancer cell metabolism: Warburg and beyond. Cell 134, 703\u2013707 (2008).","journal-title":"Cell"},{"key":"78955_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-42118-6_1","volume":"207","author":"C Brault","year":"2016","unstructured":"Brault, C. & Schulze, A. The role of glucose and lipid metabolism in growth and survival of cancer cells. Recent Results Cancer Res. 207, 1\u201322 (2016).","journal-title":"Recent Results Cancer Res."},{"key":"78955_CR24","first-page":"12","volume":"15","author":"P Jhudit","year":"2016","unstructured":"Jhudit, P., Rajesh, K. D., Suveera, D., Andrea, C. & Vincent, V. H. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle 15, 12 (2016).","journal-title":"Cell Cycle"},{"key":"78955_CR25","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.cmet.2016.06.018","volume":"24","author":"C Cyril","year":"2016","unstructured":"Cyril, C. et al. Acidosis drives the reprogramming of fatty acid metabolism in cancer cells through changes in mitochondrial and histone acetylation. Cell Metab. 24, 13 (2016).","journal-title":"Cell Metab."},{"key":"78955_CR26","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1242\/jeb.00521","volume":"206","author":"A Vezzoli","year":"2003","unstructured":"Vezzoli, A., Gussoni, M., Greco, F. & Zetta, L. Effects of temperature and extracellular pH on metabolites: Kinetics of anaerobic metabolism in resting muscle by 31P- and 1H-NMR spectroscopy. J. Exp. Biol. 206, 3043\u20133052 (2003).","journal-title":"J. Exp. Biol."},{"key":"78955_CR27","doi-asserted-by":"publisher","first-page":"L188","DOI":"10.1152\/ajplung.00544.2018","volume":"317","author":"JY Lee","year":"2019","unstructured":"Lee, J. Y. et al. Extrinsic acidosis suppresses glycolysis and migration while increasing network formation in pulmonary microvascular endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 317, L188\u2013L201 (2019).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"78955_CR28","doi-asserted-by":"publisher","first-page":"e1000293","DOI":"10.1371\/journal.pgen.1000293","volume":"4","author":"JL Chen","year":"2008","unstructured":"Chen, J. L. et al. The genomic analysis of lactic acidosis and acidosis response in human cancers. PLoS Genet. 4, e1000293 (2008).","journal-title":"PLoS Genet."},{"key":"78955_CR29","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.4049\/jimmunol.0902584","volume":"184","author":"K Dietl","year":"2010","unstructured":"Dietl, K. et al. Lactic acid and acidification inhibit TNF secretion and glycolysis of human monocytes. J. Immunol. 184, 1200\u20131209 (2010).","journal-title":"J. Immunol."},{"key":"78955_CR30","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.4161\/auto.7.11.17785","volume":"7","author":"T Xu","year":"2011","unstructured":"Xu, T., Su, H., Ganapathy, S. & Yuan, Z. M. Modulation of autophagic activity by extracellular pH. Autophagy 7, 1316\u20131322 (2011).","journal-title":"Autophagy"},{"key":"78955_CR31","doi-asserted-by":"publisher","first-page":"562","DOI":"10.4161\/auto.27901","volume":"10","author":"P Pellegrini","year":"2014","unstructured":"Pellegrini, P. et al. Acidic extracellular pH neutralizes the autophagy-inhibiting activity of chloroquine: Implications for cancer therapies. Autophagy 10, 562\u2013571 (2014).","journal-title":"Autophagy"},{"key":"78955_CR32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","volume":"132","author":"B Levine","year":"2008","unstructured":"Levine, B. & Kroemer, G. Autophagy in the pathogenesis of disease. Cell 132, 27\u201342 (2008).","journal-title":"Cell"},{"key":"78955_CR33","first-page":"916","volume":"60","author":"S Walenta","year":"2000","unstructured":"Walenta, S. et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res. 60, 916\u2013921 (2000).","journal-title":"Cancer Res."},{"key":"78955_CR34","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S1476-5586(03)80005-2","volume":"5","author":"PA Schornack","year":"2003","unstructured":"Schornack, P. A. & Gillies, R. J. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors. Neoplasia 5, 135\u2013145 (2003).","journal-title":"Neoplasia"},{"key":"78955_CR35","doi-asserted-by":"publisher","first-page":"5216","DOI":"10.1158\/0008-5472.CAN-05-4193","volume":"66","author":"RA Gatenby","year":"2006","unstructured":"Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B. & Gillies, R. J. Acid-mediated tumor invasion: A multidisciplinary study. Cancer Res. 66, 5216\u20135223 (2006).","journal-title":"Cancer Res."},{"key":"78955_CR36","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00249-018-1275-5","volume":"47","author":"AM Fouad","year":"2018","unstructured":"Fouad, A. M. A kinetic view of acid-mediated tumor invasion. Eur. Biophys. J. 47, 185\u2013189 (2018).","journal-title":"Eur. Biophys. J."},{"key":"78955_CR37","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","volume":"65","author":"LA Torre","year":"2015","unstructured":"Torre, L. A. et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87\u2013108 (2015).","journal-title":"CA Cancer J. Clin."},{"key":"78955_CR38","doi-asserted-by":"publisher","first-page":"490","DOI":"10.5858\/arpa.2016-0288-SA","volume":"141","author":"X Li","year":"2017","unstructured":"Li, X., Oprea-Ilies, G. M. & Krishnamurti, U. New developments in breast cancer and their impact on daily practice in pathology. Arch. Pathol. Lab. Med. 141, 490\u2013498 (2017).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"78955_CR39","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1089\/jwh.2019.7714","volume":"28","author":"D Dinardo","year":"2019","unstructured":"Dinardo, D. & McNeil, M. New developments in breast cancer screening and treatment. J. Womens Health (Larchmt) 28, 423\u2013426 (2019).","journal-title":"J. Womens Health (Larchmt)"},{"key":"78955_CR40","doi-asserted-by":"publisher","first-page":"12070","DOI":"10.18632\/oncotarget.2514","volume":"5","author":"SC Gupta","year":"2014","unstructured":"Gupta, S. C., Singh, R., Pochampally, R., Watabe, K. & Mo, Y. Y. Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-kappaB pathway. Oncotarget 5, 12070\u201312082 (2014).","journal-title":"Oncotarget"},{"key":"78955_CR41","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","volume":"10","author":"RM Neve","year":"2006","unstructured":"Neve, R. M. et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10, 515\u2013527 (2006).","journal-title":"Cancer Cell"},{"key":"78955_CR42","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1016\/j.celrep.2016.09.069","volume":"17","author":"S Zhao","year":"2016","unstructured":"Zhao, S. et al. ATP-citrate lyase controls a glucose-to-acetate metabolic switch. Cell. Rep. 17, 1037\u20131052 (2016).","journal-title":"Cell. Rep."},{"key":"78955_CR43","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1530\/ERC-13-0132","volume":"21","author":"F Morais-Santos","year":"2014","unstructured":"Morais-Santos, F. et al. Differential sensitivities to lactate transport inhibitors of breast cancer cell lines. Endocr. Relat. Cancer 21, 27\u201338 (2014).","journal-title":"Endocr. Relat. Cancer"},{"key":"78955_CR44","doi-asserted-by":"publisher","first-page":"4182","DOI":"10.1158\/0008-5472.CAN-06-3184","volume":"67","author":"SM Gallagher","year":"2007","unstructured":"Gallagher, S. M., Castorino, J. J., Wang, D. & Philp, N. J. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res. 67, 4182\u20134189 (2007).","journal-title":"Cancer Res."},{"key":"78955_CR45","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/2049-3002-2-23","volume":"2","author":"JJ Kamphorst","year":"2014","unstructured":"Kamphorst, J. J., Chung, M. K., Fan, J. & Rabinowitz, J. D. Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate. Cancer Metab. 2, 23 (2014).","journal-title":"Cancer Metab."},{"key":"78955_CR46","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.cell.2015.07.017","volume":"162","author":"LB Sullivan","year":"2015","unstructured":"Sullivan, L. B. et al. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 162, 552\u2013563 (2015).","journal-title":"Cell"},{"key":"78955_CR47","first-page":"2","volume":"2","author":"L Jiang","year":"2016","unstructured":"Jiang, L. et al. Quantitative metabolic flux analysis reveals an unconventional pathway of fatty acid synthesis in cancer cells deficient for the mitochondrial citrate transport protein. Metab. Eng. 2, 2 (2016).","journal-title":"Metab. Eng."},{"key":"78955_CR48","doi-asserted-by":"publisher","first-page":"8117","DOI":"10.1158\/0008-5472.CAN-09-3871","volume":"70","author":"E Rysman","year":"2010","unstructured":"Rysman, E. et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res. 70, 8117\u20138126 (2010).","journal-title":"Cancer Res."},{"key":"78955_CR49","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1038\/nrc2222","volume":"7","author":"JA Menendez","year":"2007","unstructured":"Menendez, J. A. & Lupu, R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 7, 763\u2013777 (2007).","journal-title":"Nat. Rev. Cancer"},{"key":"78955_CR50","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/jcb.10708","volume":"91","author":"A Baron","year":"2004","unstructured":"Baron, A., Migita, T., Tang, D. & Loda, M. Fatty acid synthase: A metabolic oncogene in prostate cancer?. J. Cell Biochem. 91, 47\u201353 (2004).","journal-title":"J. Cell Biochem."},{"key":"78955_CR51","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ccell.2014.12.002","volume":"27","author":"ZT Schug","year":"2015","unstructured":"Schug, Z. T. et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27, 57\u201371 (2015).","journal-title":"Cancer Cell"},{"key":"78955_CR52","doi-asserted-by":"publisher","first-page":"18175","DOI":"10.1038\/srep18175","volume":"5","author":"R Gao","year":"2015","unstructured":"Gao, R. et al. Serum metabolomics to identify the liver disease-specific biomarkers for the progression of hepatitis to hepatocellular carcinoma. Sci. Rep. 5, 18175 (2015).","journal-title":"Sci. Rep."},{"key":"78955_CR53","doi-asserted-by":"publisher","first-page":"e86","DOI":"10.1002\/cpbi.86","volume":"68","author":"J Chong","year":"2019","unstructured":"Chong, J., Wishart, D. S. & Xia, J. Using metaboAnalyst 4.0 for comprehensive and integrative metabolomics data analysis. Curr. Protoc. Bioinform. 68, e86 (2019).","journal-title":"Curr. Protoc. Bioinform."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78955-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78955-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78955-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:49:47Z","timestamp":1670374187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-78955-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["78955"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-78955-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,15]]},"assertion":[{"value":"10 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21967"}}