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.

PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway

“…Yan Li et al . found that S100A10 promoted glycolysis and proliferation by activing the mTOR pathway [ 29 ]. Besides, several inhibitors of the PI3K/Akt/mTOR signaling pathway were successfully developed in drug research and their efficacy was tested in gastric cancer with significant improvement [ 30 ].…”

The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor

“…Gastric cancer is a highly invasive and aggressive malignancy; therefore, the chance of survival depends on how early it is detected [ 184 , 220 , 221 , 222 ]. However, most gastric cancers are diagnosed in late stages when symptoms begin to appear.…”

“…More recently, Li et al [ 221 ] performed an extensive analysis of S100A10 levels in gastric cancer to investigate its potential mechanism in aerobic glycolysis often used by tumor cells. The databases used in this study were Oncomine, GEPIA, Kaplan–Meier Plotter, TCGA, GEO, GSEA, and UALCAN.…”

“…Kaplan–Meier results demonstrated a significant association between high expression of S100A10 and low survival, which illustrates the potential value of S100A10 as a prognostic tool for patients with gastric cancer. Li et al [ 221 ] hypothesized that S100A10 fueled the growth and metastasis of gastric tumors through stimulation of aerobic respiration. They used GSEA and GEPIA analysis to investigate relationships between important components of the glycolysis pathway and S100A10.…”

Plasmin and Plasminogen System in the Tumor Microenvironment: Implications for Cancer Diagnosis, Prognosis, and Therapy

“…More specifically, these studies have indicated that p11 stimulates aerobic glycolysis in gastric cancer cells via activation of Src/ANXA2/AKT/mTOR signaling pathway, ultimately leading to enhanced cell proliferation and resistance to apoptosis. This is the first investigation directly implicating p11 in aerobic glycolysis [210]. Two recent studies have highlighted the importance of p11 in modulating gene expression of pluripotency factors in breast cancer stem cells (CSC).…”