Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer
Abstract
1. General Introduction
2. Mechanism of CMA
3. Targeting of Proteins for Degradation by CMA
4. Hsc70 and Its Interaction with Target Proteins
5. Assembly of the LAMP-2A/Hsc70/Protein Complexes on the Lysosomal Surface and Translocation into the Lysosomal Lumen
6. LAMP-2A—The Lysosomal Receptor for the Hsc70/Protein Complex and a Central Player in CMA
7. Visualising CMA
8. CMA Pathways and Their Pharmacological Modulation
8.1. The mTORC2/PHLPP1/AKT Pathway
8.2. The RARα Signalling Pathway and ATRA
8.3. The ERICA Pathway
8.4. Hsp90
8.5. Hsc70
8.6. LAMP-2A
8.7. Oxidative Stress
8.8. Cross-Talk between Macroautophagy and CMA
9. CMA and Cancer
9.1. Anti-Oncogenic Roles of CMA in Healthy Cells
9.2. The Roles of CMA in Malignant Neoplasias
9.2.1. Pro-Oncogenic Role of CMA in Cancer Cells
9.2.2. Glycolytic Capability
9.2.3. Cell Cycle and Proliferation
9.2.4. DNA Damage Response
10. CMA Modulation in Cancer
11. CMA, a New Target in Cancer Therapy?
12. Conclusions and Perspectives
Funding
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Method | Pros | Cons |
---|---|---|
Immunoblot of LAMP-2A | - Technically simple | - Overall estimate of CMA changes |
Quantification of CMA active lysosomes | - Technically simple | - Overall estimate of CMA changes - Methanol fixation |
Monitoring the degradation of radiolabelled long-lived protein | - Measures CMA flux | - Involves use of radioactivity - Requires inhibition of other autophagic pathways - Measures CMA and microautophagy |
Measurement of the uptake of CMA substrate by isolated lysosomes | - Reconstitution of CMA in vitro - Measures functional CMA definitively | - Requires lysosome isolation - Requires large volume of cells or tissues |
Photoswitchable/photoactivable CMA reporter | - Measures CMA flux | - Overall estimate of CMA changes - Must be complemented by other methods - Difficult to distinguish surface bound from translocated substrate |
GAPDH-Halo tag fluorescence-based method | - Measures CMA flux | - Overall estimate of CMA changes - Must be complemented by other methods - Measures CMA and microautophagy |
KFERQ Dendra reporter | - Measures CMA flux in vitro and in vivo | - Must be complemented by other methods |
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Hubert, V.; Weiss, S.; Rees, A.J.; Kain, R. Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer. Cells 2022, 11, 2562. https://doi.org/10.3390/cells11162562
Hubert V, Weiss S, Rees AJ, Kain R. Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer. Cells. 2022; 11(16):2562. https://doi.org/10.3390/cells11162562
Chicago/Turabian StyleHubert, Virginie, Sebastian Weiss, Andrew Jackson Rees, and Renate Kain. 2022. "Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer" Cells 11, no. 16: 2562. https://doi.org/10.3390/cells11162562
APA StyleHubert, V., Weiss, S., Rees, A. J., & Kain, R. (2022). Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer. Cells, 11(16), 2562. https://doi.org/10.3390/cells11162562