Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Cultures
2.2. Preparation of Cell Lysates
2.3. Tumor Samples Processing and Dot-Blot Analysis
2.4. Estimation of Protein Concentration in Lysates
2.5. Western Blot
2.6. Dot-Blot Analysis
2.7. Extraction of Biotin-Containing Proteins
2.8. Immunocytochemistry
2.9. Immunohistochemistry
2.10. Microscopic Analysis
2.11. Enzymatic Estimation of 3-Hydroxybutyrate Release in Culture Medium
2.12. LC-MS Analysis
2.13. 1H-NMR Experiment
2.14. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Hanahan, D.; Weinberg, R.A. The Hallmarks of Cancer. Cell 2000, 100, 57–70. [Google Scholar] [CrossRef] [Green Version]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fouad, Y.A.; Aanei, C. Revisiting the Hallmarks of Cancer. Am. J. Cancer Res. 2017, 7, 1016–1036. [Google Scholar] [PubMed]
- Lyssiotis, C.A.; Kimmelman, A.C. Metabolic Interactions in the Tumor Microenvironment. Trends Cell Biol. 2017, 27, 863–875. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Reina-Campos, M.; Moscat, J.; Diaz-Meco, M. Metabolism Shapes the Tumor Microenvironment. Curr. Opin. Cell Biol. 2017, 48, 47–53. [Google Scholar] [CrossRef] [PubMed]
- Lieu, E.L.; Nguyen, T.; Rhyne, S.; Kim, J. Amino Acids in Cancer. Exp. Mol. Med. 2020, 52, 15–30. [Google Scholar] [CrossRef] [PubMed]
- Peng, H.; Wang, Y.; Luo, W. Multifaceted Role of Branched-Chain Amino Acid Metabolism in Cancer. Oncogene 2020, 39, 6747–6756. [Google Scholar] [CrossRef] [PubMed]
- Sivanand, S.; Vander Heiden, M.G. Emerging Roles for Branched-Chain Amino Acid Metabolism in Cancer. Cancer Cell 2020, 37, 147–156. [Google Scholar] [CrossRef]
- Ananieva, E.A.; Wilkinson, A.C. Branched-Chain Amino Acid Metabolism in Cancer. Curr. Opin. Clin. Nutr. Metab. Care 2018, 21, 64–70. [Google Scholar] [CrossRef] [Green Version]
- Tönjes, M.; Barbus, S.; Park, Y.J.; Wang, W.; Schlotter, M.; Lindroth, A.M.; Pleier, S.V.; Bai, A.H.C.; Karra, D.; Piro, R.M.; et al. BCAT1 Promotes Cell Proliferation through Amino Acid Catabolism in Gliomas Carrying Wild-Type IDH1. Nat. Med. 2013, 19, 901–908. [Google Scholar] [CrossRef] [Green Version]
- Raffel, S.; Falcone, M.; Kneisel, N.; Hansson, J.; Wang, W.; Lutz, C.; Bullinger, L.; Poschet, G.; Nonnenmacher, Y.; Barnert, A.; et al. BCAT1 Restricts AKG Levels in AML Stem Cells Leading to IDHmut-like DNA Hypermethylation. Nature 2017, 551, 384–388. [Google Scholar] [CrossRef] [PubMed]
- Ericksen, R.E.; Lim, S.L.; McDonnell, E.; Shuen, W.H.; Vadiveloo, M.; White, P.J.; Ding, Z.; Kwok, R.; Lee, P.; Radda, G.K.; et al. Loss of BCAA Catabolism during Carcinogenesis Enhances MTORC1 Activity and Promotes Tumor Development and Progression. Cell Metab. 2019, 29, 1151–1165. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Viana, L.R.; Tobar, N.; Busanello, E.N.B.; Marques, A.C.; de Oliveira, A.G.; Lima, T.I.; Machado, G.; Castelucci, B.G.; Ramos, C.D.; Brunetto, S.Q.; et al. Leucine-Rich Diet Induces a Shift in Tumour Metabolism from Glycolytic towards Oxidative Phosphorylation, Reducing Glucose Consumption and Metastasis in Walker-256 Tumour-Bearing Rats. Sci. Rep. 2019, 9, 15529. [Google Scholar] [CrossRef] [PubMed]
- Fuchs, B.C.; Bode, B.P. Amino Acid Transporters ASCT2 and LAT1 in Cancer: Partners in Crime? Semin. Cancer Biol. 2005, 15, 254–266. [Google Scholar] [CrossRef] [PubMed]
- Bhutia, Y.D.; Babu, E.; Ramachandran, S.; Ganapathy, V. Amino Acid Transporters in Cancer and Their Relevance to “Glutamine Addiction”: Novel Targets for the Design of a New Class of Anticancer Drugs. Cancer Res. 2015, 75, 1782–1788. [Google Scholar] [CrossRef] [Green Version]
- Bröer, S.; Bröer, A. Amino Acid Homeostasis and Signalling in Mammalian Cells and Organisms. Biochem. J. 2017, 474, 1935–1963. [Google Scholar] [CrossRef] [Green Version]
- Murín, R.; Hamprecht, B. Metabolic and Regulatory Roles of Leucine in Neural Cells. Neurochem. Res. 2008, 279–284. [Google Scholar] [CrossRef]
- Holeček, M. Branched-Chain Amino Acids in Health and Disease: Metabolism, Alterations in Blood Plasma, and as Supplements. Nutr. Metab. 2018, 15, 33. [Google Scholar] [CrossRef] [Green Version]
- Nie, C.; He, T.; Zhang, W.; Zhang, G.; Ma, X. Branched Chain Amino Acids: Beyond Nutrition Metabolism. Int. J. Mol. Sci. 2018, 19, 954. [Google Scholar] [CrossRef] [Green Version]
- Xue, P.; Zeng, F.; Duan, Q.; Xiao, J.; Liu, L.; Yuan, P.; Fan, L.; Sun, H.; Malyarenko, O.S.; Lu, H.; et al. BCKDK of BCAA Catabolism Cross-Talking with the MAPK Pathway Promotes Tumorigenesis of Colorectal Cancer. EBioMedicine 2017, 20, 50–60. [Google Scholar] [CrossRef] [Green Version]
- Lee, J.H.; Cho, Y.-R.; Kim, J.H.; Kim, J.; Nam, H.Y.; Kim, S.W.; Son, J. Branched-Chain Amino Acids Sustain Pancreatic Cancer Growth by Regulating Lipid Metabolism. Exp. Mol. Med. 2019, 51, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Sperringer, J.E.; Addington, A.; Hutson, S.M. Branched-Chain Amino Acids and Brain Metabolism. Neurochem. Res. 2017, 42, 1697–1709. [Google Scholar] [CrossRef] [PubMed]
- Li, J.-T.; Yin, M.; Wang, D.; Wang, J.; Lei, M.-Z.; Zhang, Y.; Liu, Y.; Zhang, L.; Zou, S.-W.; Hu, L.-P.; et al. BCAT2-Mediated BCAA Catabolism Is Critical for Development of Pancreatic Ductal Adenocarcinoma. Nat. Cell Biol. 2020, 22, 167–174. [Google Scholar] [CrossRef]
- Suh, E.H.; Hackett, E.P.; Wynn, R.M.; Chuang, D.T.; Zhang, B.; Luo, W.; Sherry, A.D.; Park, J.M. In Vivo Assessment of Increased Oxidation of Branched-Chain Amino Acids in Glioblastoma. Sci. Rep. 2019, 9, 340. [Google Scholar] [CrossRef] [Green Version]
- Moss, J.; Lane, M.D. The Biotin-Dependent Enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 1971, 35, 321–442. [Google Scholar] [CrossRef] [PubMed]
- Bixel, M.G.; Hamprecht, B. Immunocytochemical Localization of Beta-Methylcrotonyl-CoA Carboxylase in Astroglial Cells and Neurons in Culture. J. Neurochem. 2000, 74, 1059–1067. [Google Scholar] [CrossRef] [PubMed]
- Murín, R.; Verleysdonk, S.; Rapp, M.; Hamprecht, B. Immunocytochemical Localization of 3-Methylcrotonyl-CoA Carboxylase in Cultured Ependymal, Microglial and Oligodendroglial Cells. J. Neurochem. 2006, 1393–1402. [Google Scholar] [CrossRef] [PubMed]
- Baumgartner, M.R.; Almashanu, S.; Suormala, T.; Obie, C.; Cole, R.N.; Packman, S.; Baumgartner, E.R.; Valle, D. The Molecular Basis of Human 3-Methylcrotonyl-CoA Carboxylase Deficiency. J. Clin. Investig. 2001, 107, 495–504. [Google Scholar] [CrossRef] [Green Version]
- He, J.; Mao, Y.; Huang, W.; Li, M.; Zhang, H.; Qing, Y.; Lu, S.; Xiao, H.; Li, K. Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells through Regulating GLUD1-P38 MAPK Signaling Pathway. OncoTargets Ther. 2020, 13, 7317–7327. [Google Scholar] [CrossRef]
- Liu, Y.; Yuan, Z.; Song, C. Methylcrotonoyl-CoA Carboxylase 2 Overexpression Predicts an Unfavorable Prognosis and Promotes Cell Proliferation in Breast Cancer. Biomark. Med. 2019, 13, 427–436. [Google Scholar] [CrossRef]
- Dai, W.; Feng, H.; Lee, D. MCCC2 Overexpression Predicts Poorer Prognosis and Promotes Cell Proliferation in Colorectal Cancer. Exp. Mol. Pathol. 2020, 115, 104428. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.-Y.; Zhang, X.-N.; Xu, C.-Z.; Zhou, D.-H.; Chen, J.; Liu, Z.-X.; Sun, Y.; Huang, W.; Qu, L.-S. MCCC2 Promotes HCC Development by Supporting Leucine Oncogenic Function. Cancer Cell Int. 2021, 21, 22. [Google Scholar] [CrossRef] [PubMed]
- Martinez-Outschoorn, U.E.; Lin, Z.; Whitaker-Menezes, D.; Howell, A.; Sotgia, F.; Lisanti, M.P. Ketone Body Utilization Drives Tumor Growth and Metastasis. Cell Cycle Georget. Tex 2012, 11, 3964–3971. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xiao, F.; Wang, C.; Yin, H.; Yu, J.; Chen, S.; Fang, J.; Guo, F. Leucine Deprivation Inhibits Proliferation and Induces Apoptosis of Human Breast Cancer Cells via Fatty Acid Synthase. Oncotarget 2016, 7, 63679–63689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Comerford, S.A.; Huang, Z.; Du, X.; Wang, Y.; Cai, L.; Witkiewicz, A.K.; Walters, H.; Tantawy, M.N.; Fu, A.; Manning, H.C.; et al. Acetate Dependence of Tumors. Cell 2014, 159, 1591–1602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mashimo, T.; Pichumani, K.; Vemireddy, V.; Hatanpaa, K.J.; Singh, D.K.; Sirasanagandla, S.; Nannepaga, S.; Piccirillo, S.G.; Kovacs, Z.; Foong, C.; et al. Acetate Is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases. Cell 2014, 159, 1603–1614. [Google Scholar] [CrossRef] [Green Version]
- Murín, R.; Cesar, M.; Kowtharapu, B.S.; Verleysdonk, S.; Hamprecht, B. Expression of Pyruvate Carboxylase in Cultured Oligodendroglial, Microglial and Ependymal Cells. Neurochem. Res. 2009, 34, 480–489. [Google Scholar] [CrossRef]
- Bradford, M.M. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem. 1976, 72, 248–254. [Google Scholar] [CrossRef]
- Laemmli, U.K. Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4. Nature 1970, 227, 680–685. [Google Scholar] [CrossRef]
- Brodnanova, M.; Hatokova, Z.; Evinova, A.; Cibulka, M.; Racay, P. Differential Impact of Imipramine on Thapsigargin- and Tunicamycin-Induced Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in Neuroblastoma SH-SY5Y Cells. Eur. J. Pharmacol. 2021, 902, 174073. [Google Scholar] [CrossRef]
- Brashear, A.; Cook, G.A. A Spectrophotometric, Enzymatic Assay for D-3-Hydroxybutyrate That Is Not Dependent on Hydrazine. Anal. Biochem. 1983, 131, 478–482. [Google Scholar] [CrossRef]
- Baranovicova, E.; Grendar, M.; Kalenska, D.; Tomascova, A.; Cierny, D.; Lehotsky, J. NMR Metabolomic Study of Blood Plasma in Ischemic and Ischemically Preconditioned Rats: An Increased Level of Ketone Bodies and Decreased Content of Glycolytic Products 24 h after Global Cerebral Ischemia. J. Physiol. Biochem. 2018, 74, 417–429. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Holst, J. L-Type Amino Acid Transport and Cancer: Targeting the MTORC1 Pathway to Inhibit Neoplasia. Am. J. Cancer Res. 2015, 5, 1281–1294. [Google Scholar]
- Salisbury, T.B.; Arthur, S. The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in Cancer. Int. J. Mol. Sci. 2018, 19, 2373. [Google Scholar] [CrossRef] [Green Version]
- Lu, X. The Role of Large Neutral Amino Acid Transporter (LAT1) in Cancer. Curr. Cancer Drug Targets 2019, 19, 863–876. [Google Scholar] [CrossRef] [PubMed]
- Saito, Y.; Li, L.; Coyaud, E.; Luna, A.; Sander, C.; Raught, B.; Asara, J.M.; Brown, M.; Muthuswamy, S.K. LLGL2 Rescues Nutrient Stress by Promoting Leucine Uptake in ER+ Breast Cancer. Nature 2019, 569, 275–279. [Google Scholar] [CrossRef]
- Sato, M.; Harada-Shoji, N.; Toyohara, T.; Soga, T.; Itoh, M.; Miyashita, M.; Tada, H.; Amari, M.; Anzai, N.; Furumoto, S.; et al. L-Type Amino Acid Transporter 1 Is Associated with Chemoresistance in Breast Cancer via the Promotion of Amino Acid Metabolism. Sci. Rep. 2021, 11, 589. [Google Scholar] [CrossRef] [PubMed]
- Norton, L.E.; Layman, D.K. Leucine Regulates Translation Initiation of Protein Synthesis in Skeletal Muscle after Exercise. J. Nutr. 2006, 136, 533S–537S. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kimball, S.R.; Shantz, L.M.; Horetsky, R.L.; Jefferson, L.S. Leucine Regulates Translation of Specific MRNAs in L6 Myoblasts through MTOR-Mediated Changes in Availability of EIF4E and Phosphorylation of Ribosomal Protein S6. J. Biol. Chem. 1999, 274, 11647–11652. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jewell, J.L.; Kim, Y.C.; Russell, R.C.; Yu, F.-X.; Park, H.W.; Plouffe, S.W.; Tagliabracci, V.S.; Guan, K.-L. Metabolism. Differential Regulation of MTORC1 by Leucine and Glutamine. Science 2015, 347, 194–198. [Google Scholar] [CrossRef] [Green Version]
- Zoncu, R.; Efeyan, A.; Sabatini, D.M. MTOR: From Growth Signal Integration to Cancer, Diabetes and Ageing. Nat. Rev. Mol. Cell Biol. 2011, 12, 21–35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thomas, G.V.; Tran, C.; Mellinghoff, I.K.; Welsbie, D.S.; Chan, E.; Fueger, B.; Czernin, J.; Sawyers, C.L. Hypoxia-Inducible Factor Determines Sensitivity to Inhibitors of MTOR in Kidney Cancer. Nat. Med. 2006, 12, 122–127. [Google Scholar] [CrossRef]
- Nemazanyy, I.; Espeillac, C.; Pende, M.; Panasyuk, G. Role of PI3K, MTOR and Akt2 Signalling in Hepatic Tumorigenesis via the Control of PKM2 Expression. Biochem. Soc. Trans. 2013, 41, 917–922. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, K.; Liu, P.; Wei, W. MTOR Signaling in Tumorigenesis. Biochim. Biophys. Acta 2014, 1846, 638–654. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, L.; Han, J. Branched-Chain Amino Acid Transaminase 1 (BCAT1) Promotes the Growth of Breast Cancer Cells through Improving MTOR-Mediated Mitochondrial Biogenesis and Function. Biochem. Biophys. Res. Commun. 2017, 486, 224–231. [Google Scholar] [CrossRef] [PubMed]
- Lei, M.-Z.; Li, X.-X.; Zhang, Y.; Li, J.-T.; Zhang, F.; Wang, Y.-P.; Yin, M.; Qu, J.; Lei, Q.-Y. Acetylation Promotes BCAT2 Degradation to Suppress BCAA Catabolism and Pancreatic Cancer Growth. Signal Transduct. Target. Ther. 2020, 5, 70. [Google Scholar] [CrossRef] [PubMed]
- Luo, L.; Sun, W.; Zhu, W.; Li, S.; Zhang, W.; Xu, X.; Fang, D.; Grahn, T.H.M.; Jiang, L.; Zheng, Y. BCAT1 Decreases the Sensitivity of Cancer Cells to Cisplatin by Regulating MTOR-Mediated Autophagy via Branched-Chain Amino Acid Metabolism. Cell Death Dis. 2021, 12, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Shafei, M.A.; Flemban, A.; Daly, C.; Kendrick, P.; White, P.; Dean, S.; Qualtrough, D.; Conway, M.E. Differential Expression of the BCAT Isoforms between Breast Cancer Subtypes. Breast Cancer Tokyo Jpn. 2021, 28, 592–607. [Google Scholar] [CrossRef]
- Mayers, J.R.; Torrence, M.E.; Danai, L.V.; Papagiannakopoulos, T.; Davidson, S.M.; Bauer, M.R.; Lau, A.N.; Ji, B.W.; Dixit, P.D.; Hosios, A.M.; et al. Tissue of Origin Dictates Branched-Chain Amino Acid Metabolism in Mutant Kras-Driven Cancers. Science 2016, 353, 1161–1165. [Google Scholar] [CrossRef] [Green Version]
- Crake, R.L.I.; Burgess, E.R.; Royds, J.A.; Phillips, E.; Vissers, M.C.M.; Dachs, G.U. The Role of 2-Oxoglutarate Dependent Dioxygenases in Gliomas and Glioblastomas: A Review of Epigenetic Reprogramming and Hypoxic Response. Front. Oncol. 2021, 11, 619300. [Google Scholar] [CrossRef]
- Green, C.R.; Wallace, M.; Divakaruni, A.S.; Phillips, S.A.; Murphy, A.N.; Ciaraldi, T.P.; Metallo, C.M. Branched-Chain Amino Acid Catabolism Fuels Adipocyte Differentiation and Lipogenesis. Nat. Chem. Biol. 2016, 12, 15–21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McFate, T.; Mohyeldin, A.; Lu, H.; Thakar, J.; Henriques, J.; Halim, N.D.; Wu, H.; Schell, M.J.; Tsang, T.M.; Teahan, O.; et al. Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells. J. Biol. Chem. 2008, 283, 22700–22708. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pang, J.; Liu, W.-P.; Liu, X.-P.; Li, L.-Y.; Fang, Y.-Q.; Sun, Q.-P.; Liu, S.-J.; Li, M.-T.; Su, Z.-L.; Gao, X. Profiling Protein Markers Associated with Lymph Node Metastasis in Prostate Cancer by DIGE-Based Proteomics Analysis. J. Proteome Res. 2010, 9, 216–226. [Google Scholar] [CrossRef] [PubMed]
Glioblastoma | Astrocytoma | Meningioma | Oligodendroglioma | |
---|---|---|---|---|
Number | 20 | 7 | 8 | 4 |
Age (years) | 59 ± 11 | 33 ± 15 | 59 ± 8 | 49 ± 11 |
Gender (male/female) | 11/9 | 4/3 | 3/5 | 1/3 |
Metabolite | NMR Evaluation Range From–to | NMR Peak Assignment, Confirmed by Jres and Cosy, J–Coupling Constant (Hz) |
---|---|---|
Isoleucine | 1.0124–1.027 | 0.941 (t 1; J = 7.48) |
1.0123 (d; J = 6.99) | ||
3.678 (d; J = 4.17) | ||
Leucine | 0.960–0.981 | 0.958 (d; J = 6.23) |
0.969d (d; J = 6.05) 1.679 (m) 1.720 (m) 1.749 (m) | ||
Valine | 1.030–1.065 | 0.9936 (d; J = 7.06) 1.044 (d; J = 7.06) 2.273(m) |
3.607 (d; J = 4.40) | ||
2-Oxoisocaproate | 2.600–2.628 | 0.943 (d; J = 6.63) 2.113(m) |
2.612 (d; J = 7.02) | ||
2-Oxoisovalerate | 1.126–1.137 | 1.11 (d; J = 7.05) 3.011(t) |
3-Methyl-2-Oxovalerate | 1.085–1.113 | 0.899 (t; J = 7.52) 1.104 (d; J = 6.74) |
Acetone | 2.231–2.239 | 2.235(s) |
Compound | Specific Uptake (nmol ∗ h−1 ∗ mg−1) | |||||
---|---|---|---|---|---|---|
SW1088 | A172 | SH-SY5Y | ||||
Leucine | 26 | ±1 | 19 | ±3 | 23 | ±5 |
Isoleucine | 25 | ±2 | 20 | ±2 | 22 | ±5 |
Valine | 17 | ±2 | 15 | ±5 | 17 | ±5 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gondáš, E.; Kráľová Trančíková, A.; Baranovičová, E.; Šofranko, J.; Hatok, J.; Kowtharapu, B.S.; Galanda, T.; Dobrota, D.; Kubatka, P.; Busselberg, D.; et al. Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells. Cancers 2022, 14, 585. https://doi.org/10.3390/cancers14030585
Gondáš E, Kráľová Trančíková A, Baranovičová E, Šofranko J, Hatok J, Kowtharapu BS, Galanda T, Dobrota D, Kubatka P, Busselberg D, et al. Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells. Cancers. 2022; 14(3):585. https://doi.org/10.3390/cancers14030585
Chicago/Turabian StyleGondáš, Eduard, Alžbeta Kráľová Trančíková, Eva Baranovičová, Jakub Šofranko, Jozef Hatok, Bhavani S. Kowtharapu, Tomáš Galanda, Dušan Dobrota, Peter Kubatka, Dietrich Busselberg, and et al. 2022. "Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells" Cancers 14, no. 3: 585. https://doi.org/10.3390/cancers14030585