S100A8 enhances development of glioblastoma by activation of ANXA1- mediated NF-κB pathway

Abstract

Abstract Background Glioblastoma (GBM) is one of the most malignant tumors of human. S100A8 has emerged as vital mediators in cancer. However, the expression and function of S100A8 in GBM and the mechanism involved were unclear. Methods The expression of S100A8 was detected in glioma tissue by CGGA, TCGA database and clinical sample. CCK-8, Edu, and Colony information were used to detect cell proliferation. Wound healing and Transwell assays were used to detect cell migration and invasion, respectively. We used Xenograft model to observe the effect of S100A8 on tumor growth in vivo. Finally, immunoblotting and related biological experiments were used to detected the mechanism of S100A8 regulating the development of GBM. Results We reported that S100A8 was upregulated in GBM tissues and cells, and S100A8 expression level was correlated with the survival time of GBM patients. Knockdown S100A8 in U87 promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), whereas ectopic expression of S100A8 in LN229 decreased these activities of GBM. We also showed that knockdown S100A8 decreased tumor growth of GBM in vivo, and induced survival time of mice with GBM. Mechanistically, we found that S100A8 interacted with ANXA1, and decreased ubiquitination and degradation of ANXA1, thereby inducing NF-κB activation. Conclusion This study indicated that S100A8 promoted the development of GBM via ANXA1/NF-κB pathway, suggesting that S100A8 was a potential therapeutic target for GBM.