SLC2A3 promotes macrophage infiltration by glycolysis reprogramming in gastric cancer
- PDF / 7,660,729 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 44 Downloads / 235 Views
PRIMARY RESEARCH
Cancer Cell International Open Access
SLC2A3 promotes macrophage infiltration by glycolysis reprogramming in gastric cancer Xingxing Yao1†, Zhanke He1†, Caolitao Qin2†, Xiangqian Deng1, Lan Bai2*, Guoxin Li1* and Jiaolong Shi1*
Abstract Background: Tumors display a high rate of glucose metabolism and the SLC2A (also known as GLUT) gene family may be central regulators of cellular glucose uptake. However, roles of SLC2A family in mechanism of metabolite communication with immunity in gastric cancer remains unknown. Methods: Bioinformatics analysis and IHC staining were used to reveal the expression of SLC2A3 in gastric cancer and the correlation with survival prognosis. Real-time PCR, western blots, OCR, ECAR, lactate production and glucose uptake assays were applied to determine the effect of SLC2A3 on glycolysis reprogramming. We then investigated the consequences of SLC2A3 upregulation or inhibition on aerobic glycolysis, also explored the underlying mechanism. Bioinformatics analysis and in vitro and in vivo research were used to reveal the role of SLC2A3 in macrophage infiltration and transition. Results: Here, we show that SLC2A3 acts as a tumor promoter and accelerates aerobic glycolysis in GC cells. Mechanistically, the SLC2A3-STAT3-SLC2A3 feedback loop could promote phosphorylation of the STAT3 signaling pathway and downstream glycolytic targeting genes. Moreover, SLC2A3 potentially contributes to M2 subtype transition of macrophage infiltration in the GC microenvironment. Conclusions: SLC2A3 could be used as a prognostic biomarker to determine prognosis and immune infiltration in GC and may provide an intervention strategy for GC therapy. Keywords: SLC2A3, Glycolysis reprogramming, Macrophage, Tumor microenvironment, Gastric cancer Background Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related death worldwide [1]. With symptoms that are often mistaken for other gastric diseases, many patients with GC are diagnosed when the cancer is already at an inoperable or *Correspondence: [email protected]; [email protected]; [email protected] † Xingxing Yao, Zhanke He and Caolitao Qin contributed equally to this work. 1 Department of General Surgery, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China
metastatic stage [2]. Treatment options for advanced GC are limited, while cancer progression is generally aggressive and treatment response is poor [2]. A few biomarkers have been used as therapeutic targets for advanced GC [3]. However, therapeutic outcomes remain unsatisfactory, which may be due to multiple genetic variations and changes in the microenvironment, such as altered glucose metabolism promoting gastric carcinogenesis [4]. Tumor displays hig
Data Loading...
