Dataset Information

S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.

ABSTRACT: S100 calcium-binding protein A10 (S100A10) is crucially involved in the tumorigenesis of multiple malignant tumors. Reprogrammed glucose metabolism is emerging as a hallmark of various human cancers. However, the function of S100A10 in aerobic glycolysis is unclear. The expression of S100A10 was analyzed using the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and the UALCAN cancer database. Prognostic analysis was performed using the Kaplan-Meier Plotter. The correlation between S100A10 and key glycolytic factors was assessed by GEPIA. The glycolysis level was examined by determining glucose consumption, lactate production, adenosine triphosphate production, cellular oxygen consumption rate, and extracellular acidification rate. Cell apoptosis was investigated by flow cytometry. Colony formation and BrdU assays were performed to detect cell proliferation. A subcutaneous xenograft mouse model was established to evaluate the effects of S100A10 in vivo. Gene Set Enrichment Analysis and western blotting were performed to explore the downstream signaling pathway. S100A10 was significantly upregulated in gastric cancer. Its expression was associated with poor survival. S100A10 increased glucose consumption, lactate production, and the switch from oxidative phosphorylation to aerobic glycolysis. S100A10 promoted malignant proliferation and suppressed cell apoptosis in gastric cancer. S100A10 activated the mTOR pathway by interacting with annexin A2 (ANXA2) to accelerate tumor glycolysis, resulting in tumor malignant progression. S100A10 contributed to aerobic glycolysis and accelerated malignant growth by modulating the Src/ANXA2/AKT/mTOR signaling pathway. Thus, S100A10 may have pivotal roles in gastric cancer.

SUBMITTER: Li Y

PROVIDER: S-EPMC7726224 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.

Li Yan Y Li Xiao-Yu XY Li Li-Xiang LX Zhou Ru-Chen RC Sikong Yinhe Y Gu Xiang X Jin Bi-Ying BY Li Bing B Li Yan-Qing YQ Zuo Xiu-Li XL

Frontiers in cell and developmental biology 20201126

S100 calcium-binding protein A10 (S100A10) is crucially involved in the tumorigenesis of multiple malignant tumors. Reprogrammed glucose metabolism is emerging as a hallmark of various human cancers. However, the function of S100A10 in aerobic glycolysis is unclear. The expression of S100A10 was analyzed using the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and the UALCAN cancer database. Prognostic analysis was performed using the K ...[more]

PMID: 33324631

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Project description:Aerobic glycolysis has been shown to contribute to the abnormal activation of lung fibroblasts with excessive collagen deposition in lipopolysaccharide (LPS)-induced pulmonary fibrosis. Targeting aerobic glycolysis in lung fibroblasts might therefore be considered as a promising therapeutic approach for LPS-induced pulmonary fibrosis. In the present study, the aim was to investigate whether metformin, a widely used agent for treating type 2 diabetes, could alleviate LPS-induced lung fibroblast collagen synthesis and its potential underlying mechanisms. Different concentrations of metformin were used to treat the human lung fibroblast MRC-5 cells after LPS challenge. Indicators of aerobic glycolysis in MRC-5 cells were detected by measuring glucose consumption and lactate levels in culture medium in addition to lactate dehydrogenase activity in cellular lysates. The glucose consumption, lactate levels and the lactate dehydrogenase activity were measured respectively using colorimetric/fluorometric and ELISA kits. The effects of metformin in AMP-activated protein kinase (AMPK) activation was assessed by mitochondrial complex I activity kits. Collagen I, α-smooth muscle actin (α-SMA) and collagen III were used as markers of collagen synthesis, which was measured using western blotting, whereas phosphorylated (p-) AMPK, AMPK, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and mTOR were detected by western blotting. Metformin significantly decreased mitochondrial complex I activity and upregulated the expression of p-AMPK/AMPK protein in a concentration-dependent manner. Furthermore, the aerobic glycolysis mediated by PFKFB3 and collagen synthesis in LPS-treated MRC-5 cells was gradually inhibited with increasing concentrations of metformin. However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively. Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway.

Dataset Information

S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.

Publications

S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.

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