Author:
Gonzalez-Morena Juan M.,Escudeiro-Lopes Sara,Ferreira-Mendes Jessica Mariane,Jakoube Pavel,Cutano Valentina,Vinaixa-Forner Judith,Kralova Viziova Petra,Hartmanova Andrea,Sedlacek Radislav,Machado Susana,Malcekova Beata,Keckesova Zuzana
Abstract
Abstract
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.
Funder
IOCB Postdoctoral Fellowship
Czech Academy of Sciences
Czech Science Foundation
EMBO Installation Grant
IOCB MSCA Mobility III
EXCELES
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Biochemistry (medical),Cell Biology,Clinical Biochemistry,Pharmaceutical Science,Pharmacology
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