C-Myc在胰腺癌发生、发展中的作用  

Role of C-Myc in the Development and Progression of Pancreatic Cancer

作　　者：朱俊逸 余绮旻 石佳娜 郑水莲[2] 黄萍 吴秀蓉 杨秀丽[2] ZHU Junyi;YU Qimin;SHI Jiana;ZHENG Shuilian;HUANG Ping;WU Xiurong;YANG Xiuli(Taizhou Hospital of Zhejiang Province,Taizhou 317000,China;Clinical Pharmacy Center,Department of Pharmacy,Zhejiang Provincial People’s Hospital/Affiliated People’s Hospital,Hangzhou Medical College,Hangzhou 310034,China)

机构地区：[1]浙江省台州医院,浙江台州317000 [2]浙江省人民医院/杭州医学院附属人民医院药学部,临床药学研究中心,杭州310034

出　　处：《中国现代应用药学》2024年第11期1577-1590,共14页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省自然科学基金项目(LYY19H310009);台州市科学技术局科技计划项目(21ywa11)。

摘　　要：KRAS突变诱导的胰腺癌展现出较高的发生率、复发率及死亡风险。C-Myc位于KRAS下游,可参与多种致癌途径与胰腺癌的信号传导通路的调节,C-Myc的过度表达促进胰腺癌细胞的有氧糖酵解和谷氨酰胺的摄取,促进细胞代谢和增殖,是驱动胰腺癌进展及维持的重要因素,并与化疗及免疫治疗耐药性有关。C-Myc还与细胞周期蛋白依赖性激酶(CDK)、非编码RNA等相互作用,调控胰腺癌增殖、发展和转移过程。因此靶向C-Myc被认为是治疗胰腺癌的有效策略。C-Myc的激活依赖于与其伴侣MAX的异二聚化,随后通过与经典E-Box序列5’-CACGTG-3’结合而发挥功能,研究证明直接靶向C-Myc可抑制胰腺癌的生长,如促进C-Myc的降解、抑制C-Myc/MAX结合以及阻碍C-Myc/MAX与EBox的结合。但由于其蛋白结构的特性,导致C-Myc的直接靶向面临一定的困难,间接靶向C-Myc为治疗胰腺癌提供了新的策略,通过抑制C-Myc的转录和翻译,C-Myc-MAX异源二聚化,促进C-Myc的泛素化和降解可间接靶向C-Myc从而影响胰腺癌的发生、发展及转移。Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence,recurrence and mortality.C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer.Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells,promotes cell metabolism and proliferation,is an important factor driving the progress and maintenance of pancreatic cancer,and is related to chemotherapy and immunotherapy drug resistance.C-Myc also interacts with cell cyclin-dependent kinase(CDK)and non-coding RNA to regulate the proliferation,development and metastasis of pancreatic cancer.Therefore,targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer.The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’.Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc,inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box.However,direct targeting has been proved challenging because of its special protein structure.Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer.C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc,C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc,thus affects the occurrence,development and metastasis of pancreatic cancer.

关 键 词：胰腺癌 KRAS 靶向C-Myc 直接靶向 间接靶向 泛素化 

分 类 号：R961[医药卫生—药理学]