Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-01-02 , DOI: 10.1007/s10565-020-09574-w Dan Fang 1 , Chengfei Zhang 1 , Ping Xu 1 , Yinhua Liu 2 , Xiao Mo 1 , Qi Sun 1 , Alaa Abdelatty 1, 3 , Chao Hu 1 , Haojun Xu 1 , Guoren Zhou 4 , Hongping Xia 1, 2, 3, 4 , Linhua Lan 3
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The S100 protein family genes play a crucial role in multiple stages of tumorigenesis and progression. Most of S100 genes are located at chromosome locus 1q21, which is a region frequently rearranged in cancers. Here, we examined the expression of the S100 family genes in paired pancreatic ductal adenocarcinoma (PDAC) samples and further validated the expression of S100A16 by immunohistochemistry staining. We found that S100A16 is significantly upregulated in clinical PDAC samples. However, its roles in PDAC are still unclear. We next demonstrated that S100A16 promotes PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induces PDAC cell cycle arrest in the G2/M phase and apoptosis. Furthermore, we also demonstrated that S100A16 promotes PDAC cell proliferation, migration, and invasion via AKT and ERK1/2 signaling in a fibroblast growth factor 19 (FGF19)-dependent manner. Taken together, our results reveal that S100A16 is overexpressed in PDAC and promotes PDAC progression through FGF19-mediated AKT and ERK1/2 signaling, suggesting that S100A16 may be a promising therapeutic target for PDAC.
Graphical abstract
中文翻译：
S100A16 通过 FGF19 介导的 AKT 和 ERK1/2 通路促进胰腺癌的转移和进展
S100 蛋白家族基因在肿瘤发生和进展的多个阶段中起着至关重要的作用。大多数 S100 基因位于染色体基因座 1q21，这是一个在癌症中经常重排的区域。在这里，我们检测了配对胰腺导管腺癌 (PDAC) 样本中 S100 家族基因的表达，并通过免疫组织化学染色进一步验证了 S100A16 的表达。我们发现 S100A16 在临床 PDAC 样本中显着上调。然而，它在 PDAC 中的作用仍不清楚。我们接下来证明了 S100A16 在体外和体内均促进 PDAC 细胞增殖、迁移、侵袭和转移。S100A16 的敲低诱导 PDAC 细胞周期停滞在 G2/M 期和细胞凋亡。此外，我们还证明 S100A16 促进 PDAC 细胞增殖、迁移、并通过 AKT 和 ERK1/2 信号以成纤维细胞生长因子 19 (FGF19) 依赖性方式侵袭。总之，我们的结果表明，S100A16 在 PDAC 中过表达，并通过 FGF19 介导的 AKT 和 ERK1/2 信号传导促进 PDAC 进展，这表明 S100A16 可能是 PDAC 的一个有希望的治疗靶点。
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