S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.
S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.
复制标题
S100A10 通过激活 mTOR 信号通路加速胃癌的有氧糖酵解和恶性生长
DOI：
10.3389/fcell.2020.559486
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Zuo XL
中科院分区：
文献类型：
--
作者：
Li Y;Li XY;Li LX;Zhou RC;Sikong Y;Gu X;Jin BY;Li B;Li YQ;Zuo XL
S100钙结合蛋白A10（S100 A10）在多种恶性肿瘤的发生中起着重要作用。重新编程的葡萄糖代谢正在成为各种人类癌症的标志。然而，S100 A10在有氧糖酵解中的功能尚不清楚。使用Oncomine数据库、基因表达谱交互分析（GEPIA）、癌症基因组图谱（TCGA）和UALCAN癌症数据库分析S100 A10的表达。使用Kaplan-Meier绘图仪进行预后分析。通过GEPIA评估S100 A10与关键糖酵解因子之间的相关性。通过测定葡萄糖消耗、乳酸产生、三磷酸腺苷产生、细胞耗氧速率和细胞外酸化速率来检查糖酵解水平。流式细胞仪检测细胞凋亡。进行集落形成和BrdU测定以检测细胞增殖。建立皮下异种移植小鼠模型，以评价S100 A10的体内作用。通过基因组富集分析和蛋白质印迹分析来探索下游信号通路。S100 A10在胃癌中表达显著上调。它的表达与生存率低有关。S100 A10增加葡萄糖消耗、乳酸产生以及从氧化磷酸化到有氧糖酵解的转变。S100 A10促进胃癌细胞恶性增殖，抑制胃癌细胞凋亡。S100 A10通过与膜联蛋白A2（ANXA 2）相互作用激活mTOR通路，加速肿瘤糖酵解，导致肿瘤恶性进展。S100 A10通过调节Src/ANXA 2/AKT/mTOR信号通路促进有氧糖酵解并加速恶性肿瘤生长。因此，S100 A10可能在胃癌中起关键作用。
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.