Tumor Suppressors
Head: Zuzana Keckešová
Prague node
HOME INSTITUTION
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
It’s important to see the other side of the coin!
- Mission: Discover and characterize new tumor suppressor pathways.
- Vision: Therapeutic reactivation of tumor suppressor pathways.
Cancer represents one of the main health problems worldwide, being the second leading cause of death globally. While cancer can affect many different parts of the body with high frequencies, some types of cancer are extremely rare. This points to the possibility that some tissue-types have already devised ways of countering cancer formation, and could provide us with novel insights into the prevention and/or treatment of cancer thus serving as a great source for uncovering new tumour suppressor pathways. This approach was successfully tested and led to creation of a list of 87 genes with increased probability of being effective tumour suppressors (Keckesova et al., Nature, 2017). One of these genes, called LACTB (Lactamase B-like), was subsequently shown to be a highly potent mitochondrial tumour suppressor that acts through induction of cancer cell death and cancer cell differentiation. This study opened new avenues for research and created many exciting questions that we would like to address in our current research, which would reveal novel cell-cycle, cell-state and cell-energy regulatory mechanisms in human cancer cells.
SELECTED PUBLICATIONS
- Gonzalez-Morena, J. M.; Escudeiro-Lopes, S.; Ferreira-Mendes, J. M.; Jakoube, P.; Cutano, V.; Vinaixa-Forner, J.; Kralova Viziova, P.; Hartmanova, A.; Sedlacek, R.; Machado, S.; Malcekova, B.; Keckesova, Z. LACTB induces cancer cell death through the activation of the intrinsic caspase-independent pathway in breast cancer. Apoptosis, 2023 Feb;28(1-2):186-198. DOI: 10.1007/s10495-022-01775-4
- Cutano, V.; Ferreira Mendes, J.M.; Escudeiro-Lopes, S.; Machado, S.; Vinaixa Forner, J.; Gonzales-Morena, J.M.; Prevorovsky, M.; Zemlianski, V.; Feng, Y.; Kralova Viziova, P.; Hartmanova, A.; Malcekova, B.; Jakoube, P.; Iyer, S.; Keckesova, Z. LACTB exerts tumor suppressor properties in epithelial ovarian cancer through regulation of Slug. Life Sci Alliance. 2022 Nov 14;6(1):e202201510. Print 2023 Jan. DOI: 10.26508/lsa.202201510
- Jakoube P, Cutano V, González-Morena JM, Keckesova Z. Mitochondrial Tumor Suppressors-The Energetic Enemies of Tumor Progression. Cancer Res. 2021 Sep 15;81(18):4652-4667. DOI: 10.1158/0008-5472.CAN-21-0518
- Keckesova Z, Donaher JL, De Cock J, Freinkman E, Lingrell S, Bachovchin DA, Bierie B, Tischler V, Noske A, Okondo MC, Reinhardt F, Thiru P, Golub TR, Vance JE, Weinberg RA. LACTB is a tumour suppressor that modulates lipid metabolism and cell state. Nature. 2017 Mar 30;543(7647):681-686. DOI: 10.1038/nature21408
- Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, Reinhardt F, Itzkovitz S, Noske A, Zürrer-Härdi U, Bell G, Tam WL, Mani SA, van Oudenaarden A, Weinberg RA. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 2012 Mar 2;148(5):1015-28. DOI: 10.1016/j.cell.2012.02.008
- Dongre A, Rashidian M, Reinhardt F, Bagnato A, Keckesova Z, Ploegh HL, Weinberg RA. Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas. Cancer Res. 2017 Aug 1;77(15):3982-3989. DOI: 10.1158/0008-5472.CAN-16-3292
COLLABORATION WITHIN THE NICR
Jan Brábek
(Prague node, Faculty of Science CU)
Vítězslav Bryja
(Brno node, Faculty of Science MU)
SPECIALIZED EXPERTISE AND TECHNOLOGY
Biological 2D, 3D models for the study of cell differentiation
Cellular platforms for searching for therapeutic compounds
Real time live cell microscopy (light and flueorescent)
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
Biotechnology and Biomedicine Centre of the Czech Academy of Sciences and the Charles University BIOCEV