JPH3调控糖酵解和肿瘤干细胞干性参与结肠癌进展的作用机制研究

肿瘤细胞在有氧条件下以糖酵解而非氧化磷酸化提供能量，这种能量谢途径被称为有氧糖酵解或Warburg效应，能够使肿瘤细胞获得生存优势，是肿瘤最为重要的特征之一。同时，有氧糖酵解可能影响肿瘤细胞干性，是导致肿瘤对放化疗耐受的重要原因，其核心机制尚不明确。我们前期首次发现：（一）JPH3基因是潜在的促癌基因，目前国际上尚无报道；（二）JPH3显著促进结肠癌有氧糖酵解；（三）JPH3维持结肠癌肿瘤干细胞特性，是潜在的肿瘤干性调控基因。（四）JPH3可能调控了Wnt/beta-catenin信号通路，参与了有氧糖酵解和肿瘤干性维持过程。据此我们推测，JPH3可能作为信号串话因子（cross talk）参与了结肠癌能量代谢和干性调控的协调作用，其机制有待明确。本项目拟通过体内外实验，初步揭示JPH3的肿瘤学功能和调控机制，发现和验证关键的肿瘤标志物和干预靶点。

Tumor cells mainly rely on glycolysis rather than oxidative phosphorylation in the mitochondria to generate energy even in the presence of oxygen, the energy reprogramming of which is termed as aerobic glycolysis or Warburg effect. Warburg effect could make tumor cells sustain proliferative advantage and served as one of the most emerging tumor hallmarkers. The aerobic glycolysis may modulate tumor stemness and cause chemoradiotherapy resistant, the underlying mechanism of which remain unclear. We previously showed that JPH3 is a potential oncogene, the role of which haven't been reported yet. JPH3 might promote aerobic glycolysis and maintain the stem cell property in colon cancer possibly through the transactivation of Wnt/beta-catenin signalling pathway. Here we proposed that JPH3 might serve as a key modulator of signalling cross talk between aerobic glycolysis and tumor stemness maintainance. In this study, we aim to elucidate the function and underlying mechanism of JPH3 in colon cancer through in vitro and in vivo experiments, which is helpful to identify critical marker and therapeutic target.