LACTB induces cancer cell death through the activation of the intrinsic caspase-independent pathway in breast cancer

0563865 - ÚOCHB 2024 RIV NL eng J - Článek v odborném periodiku
Gonzalez-Morena, Juan M. - Escudeiro-Lopes, Sara - Ferreira Mendes, Jessica Marianne - Jakoubě, Pavel - Cutano, Valentina - Vinaixa Forner, Judith - Králová Viziová, Petra - Hartmanová, Andrea - Sedláček, Radislav - Machado, Susana - Malčeková, Beata - Kečkéšová, Zuzana
LACTB induces cancer cell death through the activation of the intrinsic caspase-independent pathway in breast cancer.
Apoptosis. Roč. 28, 1/2 (2023), s. 186-198. ISSN 1360-8185. E-ISSN 1573-675X
Grant CEP: GA ČR(CZ) GJ18-24473Y; GA MŠMT(CZ) EF19_074/0016322; GA MŠMT LX22NPO5102; GA MŠMT(CZ) LM2018126; GA MŠMT EF18_046/0015861
Institucionální podpora: RVO:61388963 ; RVO:68378050
Klíčová slova: LACTB * apoptosis * cell death * caspases * mitochondria * breast cancer * cell cycle arrest
Obor OECD: Biochemistry and molecular biology; Cell biology (UMG-J)
Impakt faktor: 7.2, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1007/s10495-022-01775-4

Background LACTB was recently identified as a mitochondrial tumour suppressor that negatively affects cancer cell proliferation by inducing cell death and/or differentiation, depending on the cell type and tissue. However, the detailed mechanism underlying the LACTB-induced cancer cell death is largely unknown. Methods We used cell-based, either in 2D or 3D conditions, and in vivo experiments to understand the LACTB mechanisms. In this regard, protein array followed by an enrichment analysis, cell proliferation assays using different compounds, western blot analysis, flow cytometry and immunofluorescence were performed. Differences between quantitative variables following normal distribution were valuated using Student t test for paired or no-paired samples according to the experiment. For in vivo experiments differences in tumour growth were analyzed by 2-way ANOVA. Results We show, that LACTB expression leads to cell cycle arrest in G1 phase and increase of DNA oxidation that leads to activation of intrinsic caspase-independent cell death pathway. This is achieved by an increase of mitochondrial reactive oxygen species since early time points of LACTB induction. Conclusion Our work provides a deeper mechanistic insight into LACTB-mediated cancer-cell death and shows the dynamics of the cellular responses a particular tumor suppressive stimulus might evoke under different genetic landscapes.
Trvalý link: https://hdl.handle.net/11104/0335658