{"doi":"10.1073/pnas.1114168109","title":"The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis","abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by\n                    <jats:italic>KRAS</jats:italic>\n                    activation. Here we find that transcriptional activation mediated by the Gli family of transcription factors, although dispensable for pancreatic development, is required for Kras-induced proliferation and survival in primary pancreatic epithelial cells in culture and for Kras-driven pancreatic intraepithelial neoplasia and PDAC formation in vivo. Further, ectopic Gli1 activation in the mouse pancreas accelerates Kras-driven tumor formation, underscoring the importance of Gli transcription factors in pancreatic tumorigenesis. Interestingly, we demonstrate Gli-regulated I-kappa-B kinase epsilon (IKBKE) and NF-κB activity in pancreatic cancer cells and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. Together, these studies demonstrate the requirement for Gli in Kras-dependent pancreatic epithelial transformation, suggest a mechanism of Gli-NF-κB oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2012,"id":633411,"datarank":0.7278045395879427,"base_score":4.852030263919617,"endowment":4.852030263919617,"self_citation_contribution":0.7278045395879427,"citation_network_contribution":0.0,"self_endowment_contribution":0.7278045395879427,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":127,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1642209,"name":"Wilfredo E. De Jesus-Monge","orcid":null,"position":1,"is_corresponding":false},{"id":1642211,"name":"David R. Driscoll","orcid":null,"position":2,"is_corresponding":false},{"id":1299216,"name":"Victoria A. Appleman","orcid":null,"position":3,"is_corresponding":false},{"id":1156066,"name":"He Huang","orcid":"0000-0002-6602-8247","position":4,"is_corresponding":false},{"id":246159,"name":"Jennifer L. Cotton","orcid":"0000-0003-0106-1801","position":5,"is_corresponding":false},{"id":90759,"name":"David S. Klimstra","orcid":"0000-0001-8814-1702","position":6,"is_corresponding":false},{"id":1642218,"name":"Lihua J. Zhu","orcid":null,"position":7,"is_corresponding":false},{"id":599961,"name":"Karl Simin","orcid":"0000-0002-7431-0939","position":8,"is_corresponding":false},{"id":720286,"name":"Lan Xu","orcid":"0009-0009-9272-0040","position":9,"is_corresponding":false},{"id":323733,"name":"Andrew P. McMahon","orcid":"0000-0002-3779-1729","position":10,"is_corresponding":false},{"id":1183628,"name":"Brian C. Lewis","orcid":null,"position":11,"is_corresponding":false},{"id":246170,"name":"Junhao Mao","orcid":"0000-0003-1980-1177","position":12,"is_corresponding":false},{"id":860119,"name":"Mihir Rajurkar","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis","abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by\n                    <jats:italic>KRAS</jats:italic>\n                    activation. Here we find that transcriptional activation mediated by the Gli family of transcription factors, although dispensable for pancreatic development, is required for Kras-induced proliferation and survival in primary pancreatic epithelial cells in culture and for Kras-driven pancreatic intraepithelial neoplasia and PDAC formation in vivo. Further, ectopic Gli1 activation in the mouse pancreas accelerates Kras-driven tumor formation, underscoring the importance of Gli transcription factors in pancreatic tumorigenesis. Interestingly, we demonstrate Gli-regulated I-kappa-B kinase epsilon (IKBKE) and NF-κB activity in pancreatic cancer cells and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. Together, these studies demonstrate the requirement for Gli in Kras-dependent pancreatic epithelial transformation, suggest a mechanism of Gli-NF-κB oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.852030263919617,"endowment":4.852030263919617,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22493246","pmcid":"PMC3340052","openalex_id":"https://openalex.org/W1964699883","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA113896","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA155784","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R37 NS033642","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA113896-S1","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA113896","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS033642","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS033642","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK032520","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA155784","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK32520","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA130807","title":null}],"total_grants":11,"fwci":4.655,"citation_percentile":0.96020227,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":13},{"year":2014,"count":12},{"year":2015,"count":8},{"year":2016,"count":15},{"year":2017,"count":7},{"year":2018,"count":14},{"year":2019,"count":9},{"year":2020,"count":11},{"year":2021,"count":10},{"year":2022,"count":11},{"year":2023,"count":5},{"year":2024,"count":7},{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/109/17/E1038.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/109/17/E1038.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1114168109","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1114168109","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22493246","host_type":"repository"},{"url":"https://escholarship.umassmed.edu/pgfe_pp/203","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3340052","host_type":"repository"}],"fields_of_study":["Pancreatic and Hepatic Oncology Research","Hedgehog Signaling Pathway Studies","Phagocytosis and Immune Regulation"],"mesh_terms":["Animals","Pancreatic Neoplasms","Proto-Oncogene Proteins","Genes, ras","Transcription Factors","NF-kappa B","I-kappa B Proteins","Carcinoma, Pancreatic Ductal","Cell Proliferation","Mice"],"keywords":["KRAS","Pancreatic Intraepithelial Neoplasia","Pancreatic cancer","Cancer research","Carcinogenesis","Transcription factor","Biology","GLI1","Pancreas","Ectopic expression","Mediator","Adenocarcinoma","Cell culture","Cancer","Endocrinology","Colorectal cancer","Genetics","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T12:00:31.759389Z","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":[]}