Fructose is an important alternative carbon source for several tumors, and GLUT5 is the major fructose transporter which mediates most of fructose uptake in cells. So far, it is unclear whether GLUT5-mediated fructose utilization is important for clear cell renal cell carcinoma (ccRCC). Here, we demonstrated that GLUT5 was highly expressed in a panel of ccRCC cell lines. High GLUT5 expression exacerbated the neoplastic phenotypes of ccRCC cells, including cell proliferation and colony formation. On the other hand, deletion of the GLUT5-encoding gene SLC2A5 dramatically attenuated cellular malignancy via activating the apoptotic pathway. Moreover, administration of 2,5-anhydro-D-mannitol (2,5-AM), a competitive inhibitor of fructose uptake, could markedly suppress ccRCC cell growth. Together, we provide a new mechanistic insight for GLUT5-mediated fructose utilization in ccRCC cells and highlight the therapeutic potential for targeting this metabolic pathway against ccRCC.

中文翻译：

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GLUT5介导的果糖利用在加剧透明细胞肾细胞癌的恶性肿瘤中的重要作用。

果糖是几种肿瘤的重要替代碳源，而GLUT5是主要的果糖转运蛋白，介导细胞中大部分果糖的摄取。到目前为止，尚不清楚GLUT5介导的果糖利用对于透明细胞肾细胞癌（ccRCC）是否重要。在这里，我们证明了GLUT5在ccRCC细胞系中高表达。高GLUT5表达加剧了ccRCC细胞的肿瘤表型，包括细胞增殖和集落形成。另一方面，编码GLUT5的基因SLC2A5的缺失通过激活凋亡途径，可显着减轻细胞恶性肿瘤。此外，施用2，5-脱水-D-甘露醇（2,5-AM）是一种果糖摄取的竞争性抑制剂，可以显着抑制ccRCC细胞的生长。在一起，我们为ccRCC细胞中GLUT5介导的果糖利用提供了新的机制，并突出了针对这种针对ccRCC的代谢途径的治疗潜力。