叉头盒蛋白D1激活细胞外信号调节激酶通路促进胰腺癌侵袭转移

doi:10.16139/j.1007-9610.2020.06.009

摘要/Abstract

摘要：

目的：研究叉头盒蛋白D1（forkhead box D1,FOXD1）在胰腺癌的表达及其通过细胞外信号调节激酶（extracellular signal-regulated kinase,ERK）介导胰腺癌侵袭转移的机制。方法：the Cancer Genome Atlas数据库内检索FOXD1在胰腺癌和正常胰腺组织内的表达并分析差异。采用聚合酶链反应检测15例胰腺癌病人癌组织FOXD1的mRNA表达。蛋白质印迹试验检测FOXD1在胰腺细胞株的表达和FOXD1敲低对上皮间质转化（epithelial-me-senchymal transition,EMT）相关蛋白质表达的影响。细胞计数盒8（CCK8）实验及Transwell细胞迁移实验检测FOXD1敲低对胰腺癌细胞增殖、迁移侵袭能力的影响。结果：FOXD1在胰腺癌组织及细胞株中呈高表达状态。敲低胰腺癌细胞株FOXD1表达后,胰腺癌细胞的增殖及迁移侵袭能力均减弱。降低FOXD1表达后EMT相关的上皮钙黏着蛋白、ERK表达升高,神经钙黏着蛋白、磷酸化ERK表达减弱。结论：FOXD1是胰腺癌的致癌基因,其通过激活ERK通路促进胰腺癌侵袭转移。

关键词: 叉头盒蛋白D1, 胰腺癌, 上皮间质转化, 细胞外信号调节激酶通路

Abstract:

Objective To study on the expression of forkhead box D1 (FOXD1) in pancreatic cancer and the mechanism of invasion and metastasis of pancreatic cancer through FOXD1 via the extracellular signal-regulated kinase (ERK) pathway. Methods We searched the database of expression of FOXD1 in both pancreatic cancer and normal pancreatic tissue from the Cancer Genome Atlas and analyzed the difference in expression of FOXD1. Expression of FOXD1 mRNA in pancreatic tissue of 15 cases with pancreatic cancer was detected using polymerase chain reaction. Expression of FOXD1 in pancreatic cancer cell lines was analyzed using Western Blot. The effect of FOXD1 knockdown on the expression of proteins associated with epithelial mesenchymal transition(EMT) was investigated using Western Blot. The effect of FOXD1 knockdown on the proliferation and invasion of pancreatic cancer cell lines were tested by cell counting kit-8 assay and Transwell assay. Results FOXD1 was highly expressed in pancreatic cancer tissues and cell lines. Knockdown of FOXD1 attenuated the proliferation and invasion of pancreatic cancer cell lines and enhanced expression of EMT associa-ted proteins including epithelial cadherin and ERK while attenuated expression of neuronal cadherin and phosphorylated ERK. Conclusions FOXD1 would be the oncogene of pancreatic cancer by promoting invasion and metastasis of pancrea-tic cancer via ERK pathway.

Key words: Forkhead box D1, Pancreatic cancer, Epithelial-mesenchymal transition, Extracellular signal-regulated kinase pathway

中图分类号:

R735.9

丁方谜, 刘振东. 叉头盒蛋白D1激活细胞外信号调节激酶通路促进胰腺癌侵袭转移[J]. 外科理论与实践, 2020, 25(06): 486-492.

DING Fangmi, LIU Zhendong. Forkhead box D1 promotes invasion and metastasis of pancreatic cancer via extracellular signal-regulated kinase pathway[J]. Journal of Surgery Concepts & Practice, 2020, 25(06): 486-492.

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