结肠癌是一种恶性程度极高的消化系统肿瘤，由于其固有的恶性增殖、转移复发等潜能，预后极差。亟待探寻结肠癌发生、发展的分子机制，以期改善不良预后。课题组前期研究发现：1.蛋白磷酸酶PP4C在结肠癌中表达升高，调控侵袭转移，预测不良预后；2.结合前期文章发表成果及预实验，提示PP4C可以调控结肠癌的糖酵解代谢；3.深入分析发现PP4C可以活化ERK，影响乏氧诱导因子HIF1α蛋白稳定性；4.机制探寻提示，PP4C与HDAC2相互作用，表观沉默双特异性磷酸酶DUSP3表达，进而活化ERK，稳定HIF1α，促进糖酵解。因此结肠癌细胞中存在“PP4C/HDAC2复合体表观沉默DUSP3转录而活化ERK/HIF1α轴”这样一个全新的分子机制，调控结肠癌恶性潜能。本项目拟阐述此信号通路的存在及上下游调控关系，明确通路影响糖酵解，维系恶性潜能,以期为逆转结肠癌的恶性潜能、改善不良预后提供诊疗靶点。

Colon cancer is a malignant gastrointestinal tumor. Due to innate proliferative and metastatic capacities, the overall survival is extremely worse. Thus, there is an urgent need for a better understanding of the biology of the disease in the hope of improving prognosis. Our previous studies demonstrated that: 1.The expression of protein phosphatase 4 catalytic subunit（PP4C）is elevated in colorectal cancer; 2.Based on our previous publications and preliminary results, PP4C was proposed to regulate aerobic glycolysis in colorectal cancer; 3.Deep analysis uncovered that PP4C could regulate stability of hypoxia inducible factor 1α (HIF1α) via ERK activation. 4.Mechanism explorations indicated that PP4C could interact with histone deacetylase 2 (HDAC2) to epigenetically silence dual specificity protein phosphatase 3 (DUSP3), leading to ERK activation and stabilization of HIF1α. Therefore, we put forward the existence of the “PP3C/HDAC2-DUSP3-ERK/ HIF1α” axis in colon cancer. The present study aims to confirm the existence of the axis, and validate the impact of the axis on glycolysis and malignancies of colon cancer, in the hope of improving malignancies and prognosis of this disease.