Tissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Heterozygous Deletion of FASN Increases Survival and Decreases the Number of Intestinal Adenomas during Apc-Driven Carcinogenesis
2.2. A Decrease in FASN Expression Is Associated with Downregulation of Pathways Linked to Cellular Proliferation, Energy Production, and Cancer-Associated Signaling
2.3. Heterozygous Deletion of FASN Alters the Levels of Diglycerides, but Does Not Change the Total Levels of Free Fatty Acid and Sphingolipid Species in Mouse Adenomas
2.4. Downregulation of FASN in Mouse Adenomas Alters the Levels of Cellular Metabolites
2.5. Deletion of FASN Alters Expression of Metabolites and Their Metabolizing Enzymes in Adenomas
2.6. Expression of CS Is Upregulated and Correlates with Expression of FASN in Colorectal Cancer
3. Discussion
4. Materials and Methods
4.1. Mouse Colonies
4.2. Survival Analysis and Tumor Number Studies
4.3. Histologic Analysis and Immunohistochemical (IHC) Staining
4.4. Western Blot Analysis
4.5. Antibodies for Western Blot and IHC Staining
4.6. RNA-Sequencing and Gene Set Enrichment Analysis
4.7. Metabolite Extraction
4.8. Sample Derivatization and Gas Chromatography-Mass Spectrometry (GC-MS) Quantification
4.9. Metabolite Analysis
4.10. Lipidomic Analysis
4.11. Reverse Phase Protein Analysis
4.12. Analysis of Correlation between FASN and Citrate Synthase (CS)
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drury, J.; Young, L.E.A.; Scott, T.L.; Kelson, C.O.; He, D.; Liu, J.; Wu, Y.; Wang, C.; Weiss, H.L.; Fan, T.; et al. Tissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer. Int. J. Mol. Sci. 2022, 23, 6510. https://doi.org/10.3390/ijms23126510
Drury J, Young LEA, Scott TL, Kelson CO, He D, Liu J, Wu Y, Wang C, Weiss HL, Fan T, et al. Tissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer. International Journal of Molecular Sciences. 2022; 23(12):6510. https://doi.org/10.3390/ijms23126510
Chicago/Turabian StyleDrury, James, Lyndsay E. A. Young, Timothy L. Scott, Courtney O. Kelson, Daheng He, Jinpeng Liu, Yuanyan Wu, Chi Wang, Heidi L. Weiss, Teresa Fan, and et al. 2022. "Tissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer" International Journal of Molecular Sciences 23, no. 12: 6510. https://doi.org/10.3390/ijms23126510