| 摘要: |
| KRAS诱导的胰腺癌展现出高的肿瘤复发及死亡风险,C-Myc位于KRAS下游,可与胰腺癌的多种致癌途径与多条信号传导通路相互调节,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CDK(细胞周期蛋白依赖性激酶),非编码RNA等相互作用,调控胰腺癌增殖,发展,转移过程。因此靶向C-Myc可能是胰腺癌治疗的有效策略。C-Myc依赖于与MAX的结合,才能与DNA 中的E-BOX结合发挥功能,研究证明直接靶向C-Myc如促进C-Myc的降解、抑制C-Myc/MAX结合以及阻碍C-Myc/MAX与E-BOX的结合均可以实现抑制胰腺癌生长的作用。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,目前已探索间接靶向C-Myc的方法实现对胰腺癌的治疗调控。间接靶向可通过破坏C-Myc-MAX异二聚化,影响C-Myc的稳定性,促进其泛素化及降解以及转录翻译的抑制等途径调控C-Myc表达,从而影响胰腺癌的发生、发展及转移。 |
| 关键词: 胰腺癌 KRAS 靶向C-Myc 直接靶向 间接靶向 泛素化 |
| DOI： |
| 分类号:R284.1；R917.101?????? |
| 基金项目:浙江省自然科学基金LYY19H310009 |
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| The role of C-Myc in the development and progression of pancreatic cancer |
|
zhujunyi
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Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
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| Abstract: |
| ABSTRACT: Pancreatic cancer induced by mutation KRAS exhibited increased 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.?Overexpressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer, which provide enough ATPs and a great deal of lipids and proteins for tumor cells proliferation and metabolism.C-Myc also interacts with CDK (cell cyclin-dependent kinase) and non-coding RNA .For these reasons，C-Myc was associated with chemoresistance and immune resistance and 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. C-Myc preferentially binds MAX to inform C-Myc-MAX heterodimer, which can be organized by the canonical E box sequence 5’-CACGTG-3’(E-BOX) and then regulated gene expression. Direct inhibition of the MYC-MAX heterodimer and targeted degradation of MYC may be a potential therapeutic strategy for treatment of pancreatic cancer. However,direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy to regulated incidence, development and metastasis of pancreatic cancer. C-Myc can be targeted through inhibiting transcription and translation of C-Myc,C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc. |
| Key words: pancreatic cancer KRAS targeting C-Myc direct targeting indirect targeting ubiquitination |
