{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:11:53Z","timestamp":1784679113193,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}]},{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}]},{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}]},{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}]},{"name":"New National Excellence Program of the Ministry of Human Capacities","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018818","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Semmelweis Scientific and Innovation Fund","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}]},{"name":"Semmelweis Scientific and Innovation Fund","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}]},{"name":"Semmelweis Scientific and Innovation Fund","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}]},{"name":"Semmelweis Scientific and Innovation Fund","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}]},{"name":"Semmelweis Scientific and Innovation Fund","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}]},{"name":"Higher Education Excellence Program at Semmelweis University","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}]},{"name":"Higher Education Excellence Program at Semmelweis University","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}]},{"name":"Higher Education Excellence Program at Semmelweis University","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}]},{"name":"Higher Education Excellence Program at Semmelweis University","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}]},{"name":"Higher Education Excellence Program at Semmelweis University","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}]},{"name":"Hungarian National Research, Development and Innovation Office (NKFIH)","award":["\u00daNKP_18-3-III-SE-24"],"award-info":[{"award-number":["\u00daNKP_18-3-III-SE-24"]}]},{"name":"Hungarian National Research, Development and Innovation Office (NKFIH)","award":["NKFI-FK-128404"],"award-info":[{"award-number":["NKFI-FK-128404"]}]},{"name":"Hungarian National Research, Development and Innovation Office (NKFIH)","award":["STIA-KFI-2020"],"award-info":[{"award-number":["STIA-KFI-2020"]}]},{"name":"Hungarian National Research, Development and Innovation Office (NKFIH)","award":["ED_17-1-2017-0009"],"award-info":[{"award-number":["ED_17-1-2017-0009"]}]},{"name":"Hungarian National Research, Development and Innovation Office (NKFIH)","award":["NVKP_16-1-2016-0004"],"award-info":[{"award-number":["NVKP_16-1-2016-0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as \u201cnormal\u201d control. We observed higher protein expressions of the \u201calternative bioenergetic pathway\u201d elements, in correlation with the possible higher glutamine and acetate consumption in PRCC cells instead of higher glycolytic and mTOR activity in CCRCCs. Increased expression of certain metabolic pathway markers correlates with the detected differences in metabolite ratios, as well. The lower lactate\/pyruvate, lactate\/malate, and higher pyruvate\/citrate intracellular metabolite ratios in PRCC compared to CCRCC cell lines suggest that ACHN (PRCC) have lower Warburg glycolytic capacity, less pronounced pyruvate to lactate producing activity and shifted OXPHOS phenotype. However, both studied renal carcinoma cell lines showed higher mTOR activity than tubular epithelial cells cultured in vitro, the metabolite ratio, the enzyme expression profiles, and the higher mitochondrial content also suggest increased importance of mitochondrial functions, including mitochondrial OXPHOS in PRCCs. Additionally, PRCC cells showed significant mTOR inhibitor sensitivity and the used metabolic inhibitors increased the effect of rapamycin in combined treatments. Our study revealed in situ metabolic differences in mTOR and metabolic protein expression patterns of human PRCC and CCRCC tissues as well as in cell lines. These underline the importance in the development of specific new treatment strategies, new mTOR inhibitors, and other anti-metabolic drug combinations in PRCC therapy.<\/jats:p>","DOI":"10.3390\/ijms231810587","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics"],"prefix":"10.3390","volume":"23","author":[{"given":"Ildik\u00f3","family":"Krencz","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enik\u0151","family":"Vetl\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titanilla","family":"Dank\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Pet\u0151v\u00e1ri","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Moldvai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1niel","family":"Sztankovics","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Raffay","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"M\u00e9sz\u00e1ros","sequence":"additional","affiliation":[{"name":"HAS-SE Momentum Hereditary Endocrine Tumour Syndromes Research Group, Hungarian Academy of Sciences and Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-2161","authenticated-orcid":false,"given":"Endre","family":"Sebesty\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyula","family":"V\u00e9gs\u0151","sequence":"additional","affiliation":[{"name":"Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, \u00dcll\u0151i \u00fat 78, H-1082 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"P\u00e1pay","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-4794","authenticated-orcid":false,"given":"Anna","family":"Sebesty\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/annonc\/mdz056","article-title":"Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2020","volume":"30","author":"Escudier","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1158\/2159-8290.CD-18-1354","article-title":"The Metabolic Basis of Kidney Cancer","volume":"9","author":"Linehan","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.semnephrol.2018.01.006","article-title":"Metabolomics and Metabolic Reprogramming in Kidney Cancer","volume":"38","author":"Weiss","year":"2018","journal-title":"Semin. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ccr.2011.07.018","article-title":"The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels","volume":"20","author":"Tong","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Al Ahmad, A., Paffrath, V., Clima, R., Busch, J.F., Rabien, A., Kilic, E., Villegas, S., Timmermann, B., Attimonelli, M., and Jung, K. (2019). Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation. Cancers, 11.","DOI":"10.1101\/651265"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA cycle metabolites control physiology and disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41416-019-0620-5","article-title":"New aspects of amino acid metabolism in cancer","volume":"122","author":"Vettore","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.cell.2014.11.020","article-title":"Acetate dependence of tumors","volume":"159","author":"Comerford","year":"2014","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.celrep.2018.01.030","article-title":"Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity","volume":"22","author":"Kurmi","year":"2018","journal-title":"Cell Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"421","DOI":"10.18632\/aging.100937","article-title":"Genetics of renal cancer: Focus on MTOR","volume":"8","author":"Ghosh","year":"2016","journal-title":"Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"188559","DOI":"10.1016\/j.bbcan.2021.188559","article-title":"Metabolic reprogramming in renal cancer: Events of a metabolic disease","volume":"1876","author":"Chakraborty","year":"2021","journal-title":"Biochim. Biophys Acta Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12253-020-00796-1","article-title":"mTOR in Lung Neoplasms","volume":"26","author":"Krencz","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.molcel.2013.01.019","article-title":"Nutrient sensing, metabolism, and cell growth control","volume":"49","author":"Yuan","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s10555-021-10006-2","article-title":"The role of metabolic ecosystem in cancer progression\u2014metabolic plasticity and mTOR hyperactivity in tumor tissues","volume":"40","author":"Sztankovics","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"636037","DOI":"10.3389\/fcell.2021.636037","article-title":"Mechanistic Target of Rapamycin Inhibitors in Renal Cell Carcinoma: Potential, Limitations, and Perspectives","volume":"9","author":"Faes","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/KCA-180043","article-title":"The \u2018Achilles Heel\u2019 of Metabolism in Renal Cell Carcinoma: Glutaminase Inhibition as a Rational Treatment Strategy","volume":"3","author":"Hoerner","year":"2019","journal-title":"Kidney Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6539","DOI":"10.1073\/pnas.1507228112","article-title":"MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism","volume":"112","author":"Shroff","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3233\/KCA-190058","article-title":"A Review of Papillary Renal Cell Carcinoma and MET Inhibitors","volume":"3","author":"Bilen","year":"2019","journal-title":"Kidney Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5058","DOI":"10.1038\/s41598-021-84590-2","article-title":"Comprehensive metabolomic study of the response of HK-2 cells to hyperglycemic hypoxic diabetic-like milieu","volume":"11","author":"Fiehn","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"F401","DOI":"10.1152\/ajprenal.00408.2004","article-title":"High ambient glucose is effect neutral on cell death and proliferation in human proximal tubular epithelial cells","volume":"289","author":"Morais","year":"2005","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ccell.2015.12.004","article-title":"An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma","volume":"29","author":"Hakimi","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_26","first-page":"1029","article-title":"GLUT1, MCT1\/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma","volume":"32","author":"Almeida","year":"2017","journal-title":"Histol. Histopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13371","DOI":"10.18632\/oncotarget.3823","article-title":"Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma","volume":"6","author":"Lucarelli","year":"2015","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109043","DOI":"10.18632\/oncotarget.22566","article-title":"G6PD promotes renal cell carcinoma proliferation through positive feedback regulation of p-STAT3","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tabebi, M., Kumar Dutta, R., Skoglund, C., S\u00f6derkvist, P., and Gimm, O. (2022). Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010560"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41556-018-0205-1","article-title":"mTOR as a central hub of nutrient signalling and cell growth","volume":"21","author":"Kim","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mao, Z., and Zhang, W. (2018). Role of mTOR in Glucose and Lipid Metabolism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072043"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12253-019-00677-2","article-title":"Inhibition of Metabolic Shift can Decrease Therapy Resistance in Human High-Grade Glioma Cells","volume":"26","author":"Krencz","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jiang, S., Zou, Z., Nie, P., Wen, R., Xiao, Y., and Tang, J. (2015). Synergistic Effects between mTOR Complex 1\/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132880"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1038\/s41467-020-18504-7","article-title":"mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability","volume":"11","author":"Gremke","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bbabio.2016.12.003","article-title":"Metabolic synthetic lethality in cancer therapy","volume":"1858","author":"Zecchini","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","first-page":"431","article-title":"The cancer cell in vitro: A review","volume":"22","author":"Paul","year":"1962","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12943-016-0565-8","article-title":"Choosing the right cell line for renal cell cancer research","volume":"15","author":"Brodaczewska","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1074\/jbc.M117.810101","article-title":"Characterization of the interactions of potent allosteric inhibitors with glutaminase C, a key enzyme in cancer cell glutamine metabolism","volume":"293","author":"Huang","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cmet.2018.06.003","article-title":"Pan-Cancer Metabolic Signature Predicts Co-Dependency on Glutaminase and De Novo Glutathione Synthesis Linked to a High-Mesenchymal Cell State","volume":"28","author":"Daemen","year":"2018","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nrc.2016.87","article-title":"The metabolic fate of acetate in cancer","volume":"16","author":"Schug","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1159\/000487293","article-title":"Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression","volume":"45","author":"Yao","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"243.e9","DOI":"10.1016\/j.urolonc.2018.01.013","article-title":"Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma","volume":"36","author":"Zhang","year":"2018","journal-title":"Urol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ccell.2014.12.002","article-title":"Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress","volume":"27","author":"Schug","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6746","DOI":"10.1158\/0008-5472.CAN-17-0930","article-title":"Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be Exploited for Real-Time Imaging","volume":"77","author":"Habib","year":"2017","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113502","DOI":"10.18632\/oncotarget.23056","article-title":"The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation","volume":"8","author":"Bianchi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.bbalip.2018.06.005","article-title":"Glucose-derived acetate and ACSS2 as key players in cisplatin resistance in bladder cancer","volume":"1864","author":"Wen","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00149","DOI":"10.1002\/prp2.149","article-title":"Analysis of drug combinations: Current methodological landscape","volume":"3","author":"Foucquier","year":"2015","journal-title":"Pharmacol. Res. Perspect."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10587\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:30:14Z","timestamp":1760142614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":50,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810587"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810587","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,13]]}}}