CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma

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• 作者：Kexin Li ; Baofeng Xu ; Guangying Xu ; Rui Liu
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：37
• 期：1
• 页码：419-424
• 全文大小：397 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

As reported, the CC chemokine receptor 7 (CCR7) trigger a series of signaling cascades in the epithelial-mesenchymal transition (EMT) of some malignancies. Meanwhile, Twist promotes EMT in pancreatic ductal adenocarcinoma (PDAC) progression. Here, effects of Twist on CCR7-induced EMT in the PDAC were investigated in detail. The immunohistochemistry was used to detect the expression of Twist, and then, in vitro assays were applied. The expression rate of Twist was 72.0 % in PDAC samples and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When PDAC cell line PANC1 was subjected to CCL19 stimulation, the expression of p-ERK, p-AKT, Twist, N-cadherin, MMP9, and α-smooth muscle actin (α-SMA) was induced, while the GSK1120212, BEZ235, and MK2206 prohibited the increase of Twist and EMT biomarkers. For another thing, the si-Twist treatment attenuated CCL19-stimulated EMT occurrence, migration, and invasion phenotypes of PANC1 cells. In conclusion, CCR7 pathway up-regulates Twist expression via ERK and PI3K/AKT signaling to manage the EMT of PDAC. Our work allows for clinical gene or protein-targeted regimen of PDAC patients in the near future.KeywordsCCR7TwistEMTPDAC