{"doi":"10.17615/4vpg-1m16","title":"GSK-3α Promotes Oncogenic KRAS Function in Pancreatic Cancer via TAK1–TAB Stabilization and Regulation of Noncanonical NF-κB","abstract":"Mutations in KRAS drive the oncogenic phenotype in a variety of tumors of epithelial origin. The NF-κB transcription factor pathway is important for oncogenic RAS to transform cells and to drive tumorigenesis in animal models. Recently TAK1, an upstream regulator of IKK, which controls canonical NF-κB, was shown to be important for chemoresistance in pancreatic cancer and for regulating KRAS+ colorectal cancer cell growth and survival. Here we show that KRAS+ upregulates GSK-3α leading to its interaction with TAK1 to stabilize the TAK1/TAB complex to promote IKK activity. Additionally, GSK-3α is required for promoting critical non-canonical NF-κB signaling in pancreatic cancer cells. Pharmacologic inhibition of GSK-3 suppresses growth of human pancreatic tumor explants, consistent with the loss of expression of oncogenic genes such as c-myc and TERT. These data identify GSK-3α as a key downstream effector of oncogenic KRAS via its ability to coordinately regulate distinct NF-κB signaling pathways.","journal":"UNC Libraries","year":2020,"id":144154,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9411,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":613082,"name":"Willie Wilson","orcid":null,"position":1,"is_corresponding":false},{"id":544112,"name":"Albert S. Baldwin","orcid":"0000-0003-1246-1333","position":2,"is_corresponding":false},{"id":613083,"name":"Deepali Bang","orcid":null,"position":3,"is_corresponding":false},{"id":604520,"name":"Meagan B. Ryan","orcid":"0009-0002-1699-3986","position":4,"is_corresponding":false},{"id":214461,"name":"Jen Jen Yeh","orcid":"0000-0003-2542-6211","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:45.339291Z","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":[]}