An essential role for GLUT5-mediated fructose utilization in exacerbating the malignancy of clear cell renal cell carcinoma
An essential role for GLUT5-mediated fructose utilization in exacerbating the malignancy of clear cell renal cell carcinoma
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GLUT5介导的果糖利用在加剧透明细胞肾细胞癌恶性肿瘤中的重要作用
DOI：
10.1007/s10565-019-09478-4
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发表时间：
2019-10-01
影响因子：
6.1
通讯作者：
Chen, Wen-Lian
中科院分区：
文献类型：
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作者：
Jin, Xing;Liang, Yupei;Chen, Wen-Lian
果糖是多种肿瘤的重要替代碳源，而GLUT 5是介导细胞摄取大部分果糖的主要果糖转运蛋白。到目前为止，尚不清楚GLUT 5介导的果糖利用是否对透明细胞肾细胞癌（ccRCC）很重要。在这里，我们证明了GLUT 5在一组ccRCC细胞系中高度表达。高GLUT 5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，GLUT 5编码基因SLC 2A 5的缺失通过激活凋亡途径显著减弱细胞恶性肿瘤。此外，施用果糖摄取的竞争性抑制剂2，5-脱水-D-甘露醇（2，5-AM）可显著抑制ccRCC细胞生长。总之，我们为ccRCC细胞中GLUT 5介导的果糖利用提供了新的机制见解，并强调了针对ccRCC的这种代谢途径的治疗潜力。
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.