BAX Redistribution Induces Apoptosis Resistance and Selective Stress Sensitivity in Human HCC
Abstract
:1. Introduction
2. Results
2.1. HCCs Show Selection towards Low Mitochondrial BAX Levels
2.2. Distinct Molecular Alterations Drive Cancer Progression in BAX-Protected HCCs
2.3. BAX-Protected HCC Upregulate DNA Damage Repair
2.4. Mitochondrial BAX Induces Effects Mimicking Selection of BAX-Protected HCC
2.5. BAX-Specific Inhibition Increases Sensitivity to Inhibition of DNA Damage Repair
3. Discussion
4. Materials and Methods
4.1. Quantification of Western Blot Data
4.2. Patient Data
4.3. Subcellular Fractionation
4.4. Carbonate Extraction
4.5. Gene Expression Analysis
4.6. Genomic Analyses
4.7. Caspase 3/7 Assay and PARP Cleavage
4.8. Clonogenic Survival Assay
4.9. Cell Culture and BAX Expression
4.10. Preparation of Whole-Cell Lysates
4.11. Statistics, Databases and Patient Integration
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Non-Protected | ||
Functions | p-Value Range | #Molecules |
Protein Synthesis | −0.3 × 10−3–1.17 × 10−13 | 255 |
Amino Acid Metabolism | −0.57 × 10−3–1.77 × 10−11 | 42 |
Small Molecule Biochemistry | −0.57 × 10−3–1.77 × 10−11 | 285 |
Lipid Metabolism | −0.57 × 10−3–7.14 × 10−8 | 214 |
Molecular Transport | −0.57 × 10−3–7.14 × 10−8 | 262 |
BAX-Protected | ||
Functions | p-Value range | #Molecules |
RNA Post-Transcriptional Modification | −0.28 × 10−2–6.00 × 10−5 | 10 |
DNA Replication, Recombination and Repair | −0.17 × 10−2–1.46 × 10−4 | 12 |
Cell Morphology | −0.17 × 10−2–4.75 × 10−4 | 23 |
Cellular Function and Maintenance | −0.17 × 10−2–4.75 × 10−4 | 18 |
Cell Cycle | −0.17 × 10−2–4.90 × 10−4 | 24 |
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Funk, K.; Czauderna, C.; Klesse, R.; Becker, D.; Hajduk, J.; Oelgeklaus, A.; Reichenbach, F.; Fimm-Todt, F.; Lauterwasser, J.; Galle, P.R.; et al. BAX Redistribution Induces Apoptosis Resistance and Selective Stress Sensitivity in Human HCC. Cancers 2020, 12, 1437. https://doi.org/10.3390/cancers12061437
Funk K, Czauderna C, Klesse R, Becker D, Hajduk J, Oelgeklaus A, Reichenbach F, Fimm-Todt F, Lauterwasser J, Galle PR, et al. BAX Redistribution Induces Apoptosis Resistance and Selective Stress Sensitivity in Human HCC. Cancers. 2020; 12(6):1437. https://doi.org/10.3390/cancers12061437
Chicago/Turabian StyleFunk, Kathrin, Carolin Czauderna, Ramona Klesse, Diana Becker, Jovana Hajduk, Aline Oelgeklaus, Frank Reichenbach, Franziska Fimm-Todt, Joachim Lauterwasser, Peter R. Galle, and et al. 2020. "BAX Redistribution Induces Apoptosis Resistance and Selective Stress Sensitivity in Human HCC" Cancers 12, no. 6: 1437. https://doi.org/10.3390/cancers12061437