Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. DNA and shRNA Constructs
2.3. Human PDAC Tissue Microarray (TMA)
2.4. Immunofluorescence Staining and Image Acquisition
2.5. Immunohistochemistry and Scoring
2.6. Comet Assay
2.7. Cellular Viability and Colony Formation Assays
2.8. Western Blot
2.9. Statistical Analysis
3. Results
3.1. DNA Damage-Induced pSer784-VCP Levels Vary among PDAC Cell Lines
3.2. pSer784-VCP Levels Predict the Chemotherapy Effect on Genome Integrity and Sensitizing Effect of VCP Inhibitor in PDAC Cell Lines
3.3. pSer784-VCP Levels Predict Chemotherapy Effect on Cell Survival and Sensitizing Effect of VCP Inhibitor in PDAC Cell Lines
3.4. pSer784-VCP Protects PDAC Cell Lines from Chemotherapy-Induced DNA Damage and Cell Death
3.5. pSer784-VCP Levels Significantly Associate with Poor Survival of PDAC Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wang, F.; Vij, K.; Li, L.; Dodhiawala, P.; Lim, K.-H.; Shao, J. Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor. Cancers 2021, 13, 5076. https://doi.org/10.3390/cancers13205076
Wang F, Vij K, Li L, Dodhiawala P, Lim K-H, Shao J. Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor. Cancers. 2021; 13(20):5076. https://doi.org/10.3390/cancers13205076
Chicago/Turabian StyleWang, Faliang, Kiran Vij, Lin Li, Paarth Dodhiawala, Kian-Huat Lim, and Jieya Shao. 2021. "Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor" Cancers 13, no. 20: 5076. https://doi.org/10.3390/cancers13205076