Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer
作者机构：Department of Veterinary Physiology and PharmacologyTexas A&M UniversityCollege StationTX 77845United States Department of Biochemistry and BiophysicsTexas A&M UniversityCollege StationTX 77845United States Cancer InstituteCleveland ClinicClevelandOH 44195United States Department of Medical OncologyHouston Methodist Hospital Cancer CenterHoustonTX 77030United States
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2021年第27卷第38期
页 面：6387-6398页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Supported by Houston Methodist Cancer Center Innovation Award。
主 题：Specificity protein Nuclear receptor 4A1 Pancreatic cancer Transcription factors Ligand inhibitors Nuclear receptor 4A antagonists
摘 要：Specificity protein(Sp)transcription factors(TFs)Sp1,Sp3 and Sp4,and the orphan nuclear receptor 4A1(NR4A1)are highly expressed in pancreatic tumors and Sp1 is a negative prognostic factor for pancreatic cancer patient survival.Results of knockdown and overexpression of Sp1,Sp3 and Sp4 in pancreatic and other cancer lines show that these TFs are individually pro-oncogenic factors and loss of one Sp TF is not compensated by other members.NR4A1 is also a prooncogenic factor and both NR4A1 and Sp TFs exhibit similar functions in pancreatic cancer cells and regulate cell growth,survival,migration and invasion.There is also evidence that Sp TFs and NR4A1 regulate some of the same genes including survivin,epidermal growth factor receptor,PAX3-FOXO1,α5-andα6-integrins,β1-,β3-andβ4-integrins;this is due to NR4A1 acting as a cofactor and mediating NR4A1/Sp1/4-regulated gene expression through GC-rich gene promoter sites.Several studies show that drugs targeting Sp downregulation or NR4A1 antagonists are highly effective inhibitors of Sp/NR4A1-regulated pathways and genes in pancreatic and other cancer cells,and the triterpenoid celastrol is a novel dual-acting agent that targets both Sp TFs and NR4A1.
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