Evaluation of calcium-binding protein A11 promotes the carcinogenesis of hypopharygeal squamous cell carcinoma via the PI3K/AKT signaling pathway

Am J Transl Res. 2019 Jun 15;11(6):3472-3480. eCollection 2019.

Abstract

Background: The S100 gene family encodes low molecular weight proteins implicated in cancer progression. In the present study, we explored the effects and underlying mechanisms of calcium-binding protein A11 (S100A11 protein) in hypopharyngeal squamous cell carcinoma (HSCC).

Methods: RT-qPCR and western blot analysis were used to detect the mRNA and protein expression of S100A11, EGFR, MMP2, CD44, and MMP9. CCK-8, colony formation, wound healing and transwell invasion assays were performed to evaluate the effects of S100A11 on HSCC cells.

Results: In our study, we observed that the level of S100A11 expression was significantly upregulated in HSCC tissues and cell lines. S100A11 inhibition increased the effects of 5-Fu on FaDu cells proliferation in vitro. In addition, S100A11 inhibition decreased the migration ability of FaDu cells. Additionally, the expression of migration-related proteins including EGFR, MMP2, CD44, and MMP9 were down-regulated when S100A11 was knocked down. Moreover, the expression of phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR) and BCL-2 in FaDu cells were dramatically decreased.

Conclusions: Our results suggested that S100A11 could activate the PI3K/Akt/mTOR signaling pathway in HSCC tumorigenesis.

Keywords: PI3K/Akt/mTOR; S100A11; hypopharyngeal squamous cell carcinoma; migration.