S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway.
10.12122/j.issn.1673-4254.2023.05.08
- Author:
Huijie WANG
1
;
Zhengui SUN
2
;
Wenying ZHAO
1
;
Biao GENG
2
Author Information
1. Department of Oncology, First Affiliated Hospital of Wannan Medical College, Wuhu 24100, China.
2. Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Wannan Medical College, Wuhu 24100, China.
- Publication Type:Journal Article
- Keywords:
Akt-mTOR;
S100A10;
clinicopathological parameters;
glycolysis;
lung adenocarcinoma;
tumor cell invasion and proliferation
- MeSH:
Animals;
Mice;
Adenocarcinoma of Lung/pathology*;
Cell Proliferation;
Lung Neoplasms/pathology*;
Mice, Nude;
Proto-Oncogene Proteins c-akt;
Signal Transduction;
TOR Serine-Threonine Kinases;
Humans;
S100 Proteins/genetics*
- From:
Journal of Southern Medical University
2023;43(5):733-740
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.
METHODS:Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.
RESULTS:The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).
CONCLUSION:S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.
