糖代谢重编程是肿瘤的一个重要代谢特征，并参与肿瘤的发生发展。活跃的糖代谢常导致肿瘤组织中葡萄糖不足。而糖转运子GLUT5介导的果糖代谢是维持肿瘤细胞代谢活性的重要替代途径。我们前期发现，GLUT5在肾癌细胞中高表达并介导肾癌细胞的果糖摄取和利用、以及促进细胞的生长和存活。但是，该代谢通路促进肾癌生长的分子机制尚未明确。预实验发现，GLUT5介导的果糖代谢重编程可活化肾癌细胞的糖酵解和三羧酸循环以及上调ROS生成。进一步发现，该代谢通路可激活肾癌细胞的PI3K/AKT信号。综合预实验数据，我们提出科学假说：肾癌细胞高表达GLUT5，促进果糖的摄取和利用、激活糖酵解和三羧酸循环并促进ROS产生，ROS通过抑制PTEN活性而激活PI3K/AKT信号，进而促进肾癌恶性生长。本研究将为我们通过干预果糖代谢治疗肾癌提供坚实的科学依据。

Glucose metabolism reprogramming is a key hallmark of tumors and is involved in tumorigenesis and tumor progression. Hyperactive glucose metabolism usually leads to glucose scarcity in tumor tissues. Fructose metabolism mediated by the sugar transporter GLUT5 is an important alternative pathway to sustain the metabolic activity of tumor cells. We found that GLUT5 was highly expressed in renal cancer (RC) cells to facilitate fructose uptake and utilization and to promote RC cell growth and survival. However, the downstream molecular mechanism is still unclear. Our preliminary investigation revealed that GLUT5-mediated fructose metabolism activated glycolysis and TCA cycle, and increased ROS production in RC cells. Of note, GLUT5-mediated fructose metabolism enhanced PI3K/AKT signaling activity in RC cells. Based on these preliminary results, we hypothesize that increased expression of GLUT5 in RC cells elevates fructose input and utilization, and then activates glycolysis and TCA cycle. Active glycolysis and TCA cycle increase ROS production. ROS act as signaling molecules to stimulate PI3K/AKT signaling via inactivating PTEN, thus expediting the neoplastic growth of RC. This project will provide strong evidence for targeting fructose metabolism to treat RC.