{"doi":"10.1101/2022.05.20.492006","title":"PGC-1β and ERRα promote glutamine metabolism and colorectal cancer survival via transcriptional regulation of PCK2","abstract":"Abstract 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. In this study, we 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 used RNAsequencing to determine the genes regulated by both PGC-1β & ERRα and found that mitochondrial Phosphoenolpyruvate Carboxykinase 2 (PCK2) was the gene that decreased most significantly after depletion of both genes. 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. 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303371,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":995594,"name":"Thomas C. Troia","orcid":"0000-0001-8214-2034","position":1,"is_corresponding":false},{"id":716475,"name":"Chaitra Rao","orcid":"0000-0002-2834-7458","position":2,"is_corresponding":false},{"id":717289,"name":"Robert A. Svoboda","orcid":null,"position":3,"is_corresponding":false},{"id":232404,"name":"Jordan A. Berg","orcid":"0000-0002-5096-0558","position":4,"is_corresponding":false},{"id":651474,"name":"Dhananjay Shinde","orcid":"0000-0003-4682-0699","position":5,"is_corresponding":false},{"id":393120,"name":"Vinai C. Thomas","orcid":"0000-0002-7886-0727","position":6,"is_corresponding":false},{"id":566250,"name":"Robert E. Lewis","orcid":"0000-0002-3616-2971","position":7,"is_corresponding":false},{"id":566251,"name":"Kurt W. Fisher","orcid":"0000-0002-8391-390X","position":8,"is_corresponding":false},{"id":716476,"name":"Danielle E. Frodyma","orcid":"0000-0002-8120-6953","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}