Tumour biology – Tumour metabolism research group

Failures in signalling pathways could contribute to the alterations occurring in cellular metabolism of tumour cells. As a key element of signalling network, mTOR (mammalian target of rapamycin) regulates several cellular functions depending on the available nutrients, energy and other factors/the oscillating energy status, nutrient and other factor availability. Appropriate regulation of mTOR can influence cellular metabolic activity including glucose and glutamine uptake, glutaminolysis or oxidative phosphorylation, respectively. Deregulated mTOR signalling are well-known in changes leading to carcinogenesis. Our results also highlight that there is a significant correlation among high mTOR activity – especially in case it is mTORC2 complex related –, worse prognosis and therapy resistance. We study the role and importance of mTORC1 and C2 complexes in relation of therapy resistance and metabolic plasticity of tumour cells. In parallel, we investigate the tissue and metabolic heterogeneity, and additionally its potential diagnostic and therapeutic impact in a wide-range of tumour cells. Beside the characterisation of human tumour tissues, we involve in vitro and in vivo model systems in our experimental designs. During the course of previous period, we succeeded in establishing the infrastructural background of 3D bioprinting technique. Consequently, we are able to perform metabolic studies involving not only 2D and 3D cell cultures but the 3D bioprinted tissue-like structures. In relation to these, our aims are both optimising the experimental approach of metabolic adaptation and developing the pre-selection method of a better anti-tumoural agent. As a matter of course, molecular biology and analytical chemistry methods and even metabolic profiling gain important roles in these studies. Last year WES Simple (capillary-based Western blot) technique was also introduced in our laboratory unit besides the 3D bioprinting. As a novel technology, WES Simple is suitable for performing quantitative analysis even on low amount of proteins. In a collaborative work, the parameters of LC-MS measurement were set to study metabolite concentrations.

Related own publications

  • Sebestyén A, Hajdu M, Kis L, Barna G, Kopper L. Smad4-independent, PP2A-dependent apoptotic effect of exogenous transforming growth factor beta 1 in lymphoma cells. Exp Cell Res. 2007;313(15):3167-3174. doi:10.1016/j.yexcr.2007.05.028
  • Sebestyén A, Sticz TB, Márk A, et al. Activity and complexes of mTOR in diffuse large B-cell lymphomas–a tissue microarray study. Mod Pathol. 2012;25(12):1623-1628. doi:10.1038/modpathol.2012.141
  • Márk Á, Hajdu M, Váradi Z, et al. Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease–a combined tissue microarray, in vitro and in vivo study. BMC Cancer. 2013;13:250. 2013 May 22. doi:10.1186/1471-2407-13-250
  • Sebestyén A, Márk Á, Hajdu M, et al. Rapamycin can restore the negative regulatory function of transforming growth factor beta 1 in high grade lymphomas. Cytokine. 2015;73(2):219-224. doi:10.1016/j.cyto.2015.02.024
  • Hujber Z, Petővári G, Szoboszlai N, et al. Rapamycin (mTORC1 inhibitor) reduces the production of lactate and 2-hydroxyglutarate oncometabolites in IDH1 mutant fibrosarcoma cells. J Exp Clin Cancer Res. 2017;36(1):74. 2017 Jun 2. doi:10.1186/s13046-017-0544-y
  • Hujber Z, Horváth G, Petővári G, et al. GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas. J Exp Clin Cancer Res. 2018;37(1):271. 2018 Nov 7. doi:10.1186/s13046-018-0946-5
  • Petővári G, Hujber Z, Krencz I, et al. Targeting cellular metabolism using rapamycin and/or doxycycline enhances anti-tumour effects in human glioma cells. Cancer Cell Int. 2018;18:211. 2018 Dec 19. doi:10.1186/s12935-018-0710-0
  • Krencz I, Sebestyen A, Papay J, et al. Correlation between immunohistochemistry and RICTOR fluorescence in situ hybridization amplification in small cell lung carcinoma. Hum Pathol. 2019;93:74-80. doi:10.1016/j.humpath.2019.08.018
  • Petővári G, Dankó T, Krencz I, et al. Inhibition of Metabolic Shift can Decrease Therapy Resistance in Human High-Grade Glioma Cells. Pathol Oncol Res. 2020;26(1):23-33. doi:10.1007/s12253-019-00677-2
  • Sarkadi B, Meszaros K, Krencz I, et al. Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas. Cancers (Basel). 2020;12(3):599. 2020 Mar 5. doi:10.3390/cancers12030599

Members of research group

Anna Sebestyén, PhD – senior research fellow, leader of research group
László Kopper, DSc – professor emeritus
András Jeney, DSc – professor emeritus
Judit Pápay, MD, PhD – associate professor
Melinda Hajdu, MD, PhD – senior lecturer
Ildikó Krencz, MD – postdoctoral researcher, resident
Gábor Petővári – predoctoral fellow
Titanilla Dankó – PhD student
Dániel Sztankovics – PhD student
Luca Felkai, MD – PhD student
Enikő Vetlényi, MD – PhD student
Regina Raffay – technical assistant
members of Students’ Scientific Associations: Dorottya Moldvai, Annamária Bozsik, Krisztina Sipos