| Autor: |
Danielle E. Frodyma, Thomas C. Troia, Chaitra Rao, Robert A. Svoboda, Jordan A. Berg, Dhananjay D. Shinde, Vinai C. Thomas, Robert E. Lewis, Kurt W. Fisher |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancers; Volume 14; Issue 19; Pages: 4879 |
| ISSN: |
2072-6694 |
| Popis: |
Background: Previous studies have shown that Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Beta (PGC-1β) and Estrogen-Related Receptor Alpha (ERRα) are over-expressed in colorectal cancer and promote tumor survival. Methods: In this study, we use immunoprecipitation of epitope tagged endogenous PGC-1β and inducible PGC-1β mutants to show that amino acid motif LRELL on PGC-1β is responsible for the physical interaction with ERRα and promotes ERRα mRNA and protein expression. We use RNAsequencing to determine the genes regulated by both PGC-1β & ERRα and find that mitochondrial Phosphoenolpyruvate Carboxykinase 2 (PCK2) is the gene that decreased most significantly after depletion of both genes. Results: Depletion of PCK2 in colorectal cancer cells was sufficient to reduce anchorage-independent growth and inhibit glutamine utilization by the TCA cycle. Lastly, shRNA-mediated depletion of ERRα decreased anchorage-independent growth and glutamine metabolism, which could not be rescued by plasmid derived expression of PCK2. Discussion: These findings suggest that transcriptional control of PCK2 is one mechanism used by PGC-1β and ERRα to promote glutamine metabolism and colorectal cancer cell survival. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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