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 SLC2A5, is the specific fructose transporter in mammalian cells. In this study, we found that SLC2A5 is significantly upregulated in lung adenocarcinoma (LUAD) patients and overexpression of SLC2A5 is highly correlated with poor prognosis of LUAD patients. The expression of SLC2A5 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 SLC2A5 undermined cell proliferation and invasion meanwhile increased cell apoptosis. Overexpression of SLC2A5 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.
Highlights
Alteration of cellular metabolism is one of the hallmarks of cancer cells[1, 2]
SLC2A5 is overexpressed in NSCLC and its overexpression associates with poor prognosis of lung adenocarcinoma
RNA-Seq data from TCGA revealed expression of SLC2A5 was higher in both lung adenocarcinoma and squamous cell carcinoma (SCC) compared to normal lung tissue (Fig. 1a)
Summary
Alteration of cellular metabolism is one of the hallmarks of cancer cells[1, 2]. Mutations of oncogenes and tumor suppressor genes drive somatic cells to tumor cells, which reprogram the intracellular metabolic pathways to provide building blocks and energy required for rapid cell proliferation or survival in harsh environment. The expression of SLC2A5 is elevated in breast cancer cell lines MCF7 and MDA-MB-231, and is associated with higher fructose uptake rate[17]. The expression of SLC2A5 determined fructose uptake in LUAD cells. Lack of SLC2A5 significantly affected cell proliferation in fructose-containing medium (Fig. 3b).
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