PFK1介导的表观遗传调控在癌症发生、发展中的作用及机制

磷酸果糖激酶亚型1（PFK1）是糖酵解过程中最重要的限速酶之一，其活性被严格调控。但在很多肿瘤细胞中，PFK1受癌基因调控，都有着异常的表达和活性。最近研究报道PFK1的糖基化，通过对肿瘤细胞代谢通路的重编程，赋予肿瘤细胞独特的生长优势，从而进一步强调了PFK1在肿瘤发生中的重要性。然而，PFK1是否能转运入细胞核，及其在细胞核内的功能还未见报道。本项目作为申请人前期工作的拓展，在预实验的基础上，围绕PFK1的细胞核内功能，重点阐述PFK1调控组蛋白H3翻译后修饰的机制，并揭示该调控在EGFR促进的肿瘤发生中的作用。本项目的研究，将揭示PFK1通过调控表观遗传促进肿瘤生长的新机制，并有助于深入理解癌症发生、发展中代谢调控的重要作用，并为寻找新的癌症生物标志以及治疗靶点提供理论指导。

Phosphofructokinase 1 (PFK1) is one of the most important rate-limiting enzymes, whose activity is tightly regulated. But many cancers have increased expression and activity of PFK1, driven by oncogenes. Recent study showed that glycosylation of PFK1 confers growth advantage to tumor cells by metabolic reprogram, highlighting the importance of PFK1 in tumorigenesis. However, nuclear translocation and functions of nuclear PFK1 remain unclear. Extended from applicant's previous work and based on the preliminary data, this project will focus on the functions of nuclear PFK1, demonstrating the roles and mechanisms of the regulation of posttranslational modifications of Histone H3 by PFK1 in EGFR-promoted tumorigenesis, which will facilitate understanding the importance of metallic regulation in tumorigenesis and provide the molecular basis for searching new biomarkers and therapeutic targets.