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通过增强果糖利用促进肺腺癌细胞生长和转移。

promotes lung adenocarcinoma cell growth and metastasis by enhancing fructose utilization.

作者信息

Weng Yuanyuan, Fan Xueyu, Bai Yongfeng, Wang Siwei, Huang Hui, Yang Huimin, Zhu Jin, Zhang Feng

机构信息

1Department of Clinical Laboratory, Core Facility, Quzhou People's Hospital, Quzhou, Zhejiang China.

2Department of Pharmacology, Quzhou People's Hospital, Quzhou, Zhejiang China.

出版信息

Cell Death Discov. 2018 Feb 26;4:38. doi: 10.1038/s41420-018-0038-5. eCollection 2018 Dec.

DOI:10.1038/s41420-018-0038-5
PMID:29531835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5841403/
Abstract

The metabolism of cancer cells is highly plastic. Cancer cells can change their preference for nutrient uptake under nutrient stress. Fructose is one of the most common carbohydrates in diet and its metabolism is also involved in the development and progression of tumors. GLUT5, encoded by , is the specific fructose transporter in mammalian cells. In this study, we found that is significantly upregulated in lung adenocarcinoma (LUAD) patients and overexpression of is highly correlated with poor prognosis of LUAD patients. The expression of determined fructose uptake and utilization efficacy in LUAD cells. GLUT5 is critical for the survival of LUAD cells in fructose-containing culture medium. Depletion of undermined cell proliferation and invasion meanwhile increased cell apoptosis. Overexpression of enhances cell proliferation, migration, invasion, and tumorigenic. Compared to glucose, fructose is prone to strengthen intracellular-free fatty acid accumulation and ATP production. Moreover, inhibition of GLUT5 by specific small chemical inhibitor sensitizes LUAD cells to paclitaxel treatment. Taken together, our results suggest that GLUT5 could be a potential target alone or combination with other treatment for lung cancer therapy.

摘要

癌细胞的代谢具有高度可塑性。在营养应激状态下,癌细胞会改变其对营养物质摄取的偏好。果糖是饮食中最常见的碳水化合物之一,其代谢也参与肿瘤的发生和发展。由[基因名称]编码的GLUT5是哺乳动物细胞中的特异性果糖转运蛋白。在本研究中,我们发现[基因名称]在肺腺癌(LUAD)患者中显著上调,且其过表达与LUAD患者的不良预后高度相关。[基因名称]的表达决定了LUAD细胞中果糖的摄取和利用效率。GLUT5对LUAD细胞在含果糖培养基中的存活至关重要。[基因名称]的缺失削弱了细胞增殖和侵袭,同时增加了细胞凋亡。[基因名称]的过表达增强了细胞增殖、迁移、侵袭和致瘤性。与葡萄糖相比,果糖更容易增强细胞内游离脂肪酸的积累和ATP的产生。此外,用特异性小分子化学抑制剂抑制GLUT5可使LUAD细胞对紫杉醇治疗敏感。综上所述,我们的结果表明,GLUT5可能是肺癌治疗的一个潜在单独靶点或与其他治疗联合的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/a6bcbed0b3b2/41420_2018_38_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/e9a100a77ac1/41420_2018_38_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/5961b8f7dd52/41420_2018_38_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ca70eff26903/41420_2018_38_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ecb2d9268c38/41420_2018_38_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ffdc572e4014/41420_2018_38_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/c2be8a6a7860/41420_2018_38_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/a6bcbed0b3b2/41420_2018_38_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/e9a100a77ac1/41420_2018_38_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/5961b8f7dd52/41420_2018_38_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ca70eff26903/41420_2018_38_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ecb2d9268c38/41420_2018_38_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/ffdc572e4014/41420_2018_38_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/c2be8a6a7860/41420_2018_38_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c34/5841403/a6bcbed0b3b2/41420_2018_38_Fig7_HTML.jpg

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