Wang Chengyu, Lin Chen, Tao Qilei, Zhao Shuwei, Liu Huanhai, Li Li
Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
Am J Transl Res. 2019 Jun 15;11(6):3472-3480. eCollection 2019.
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).
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.
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.
Our results suggested that S100A11 could activate the PI3K/Akt/mTOR signaling pathway in HSCC tumorigenesis.
S100基因家族编码与癌症进展相关的低分子量蛋白质。在本研究中，我们探讨了钙结合蛋白A11（S100A11蛋白）在下咽鳞状细胞癌（HSCC）中的作用及潜在机制。
采用RT-qPCR和蛋白质印迹分析检测S100A11、表皮生长因子受体（EGFR）、基质金属蛋白酶2（MMP2）、CD44和基质金属蛋白酶9（MMP9）的mRNA和蛋白质表达。进行细胞计数试剂盒-8（CCK-8）、集落形成、伤口愈合和Transwell侵袭实验，以评估S100A11对HSCC细胞的影响。
在我们的研究中，我们观察到S100A11在HSCC组织和细胞系中的表达水平显著上调。抑制S100A11可增强5-氟尿嘧啶（5-Fu）对FaDu细胞体外增殖的抑制作用。此外，抑制S100A11可降低FaDu细胞的迁移能力。此外，当S100A11被敲低时，包括EGFR、MMP2、CD44和MMP9在内的迁移相关蛋白的表达下调。此外，FaDu细胞中磷酸化磷脂酰肌醇-3激酶（p-PI3K）、磷酸化蛋白激酶B（p-Akt）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）和B细胞淋巴瘤-2（BCL-2）的表达显著降低。
我们的结果表明，S100A11可能在下咽鳞状细胞癌发生过程中激活PI3K/Akt/mTOR信号通路。
