转录因子Fra-1在肿瘤进展中的调控机制及其作为治疗靶点的临床意义  

Effect of transcriptional factor Fra-1 on control of tumor progression and the clinical implications as a therapeutic target

作　　者：裘洪梅[1] 白晓彦 QIU Hongmei;BAI Xiaoyan(Medical College of Dalian University,Dalian 116622,China)

机构地区：[1]大连大学医学院,大连116622

出　　处：《生命的化学》2022年第5期1000-1009,共10页Chemistry of Life

基　　金：国家自然科学基金项目(81802758)。

摘　　要：在AP-1二聚体复合物中,由FOSL1编码的转录因子Fra-1在人类肿瘤的发生和进展中发挥了至关重要的作用,它在大多数实体肿瘤中呈现高表达,有望成为一个极具价值的治疗靶点。本文首先总结了癌细胞内调控FOSL1表达的分子机制,包括FOSL1基因的转录调控、转录后修饰以及Fra-1蛋白的翻译后修饰过程。其次,系统阐述了Fra-1在多种癌细胞中发挥的作用以及相应的调控机制,特别是Fra-1及其靶基因产物在癌细胞增殖、存活、上皮间质转化以及转移过程中发挥的重要功能。最后,探讨了以Fra-1为靶点的靶向治疗的研究进展,以及Fra-1在癌症靶向治疗耐药过程中的作用,旨在为开发抗Fra-1药物指导癌症的临床诊疗提供依据。Transcription factor Fra-1,encoded by FOSL1 gene among the AP-1 dimeric complex,plays an important role in carcinogenesis and progression of tumor,and it is overexpressed in most solid tumors,so it might be a valuable target for cancer therapy.In the review,we summarize the findings related to the control of Fra-1 expression in cancer cell,including transcription,posttranscription regulation,and posttranslational modification for protein stability.Then,we systematically demonstrate the Fra-1-based gene regulatory net to control cell proliferation,survival,epithelial-mesenchymal transitions and metastasis in various cancer types.Finally,the research progress of Fra-1 as therapeutic target and resistance to targeted therapies are discussed,aimed at providing a basis of the anti-Fra-1 drugs for the clinical diagnosis and treatment of cancers.

关 键 词：Fra-1 转录调控 肿瘤 靶向治疗 

分 类 号：R730.2[医药卫生—肿瘤]