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Isthmin-1通过上皮-间质转化促进胰腺癌转移侵袭的机制研究

张新宇 徐智超 王振涛 陈庆 秦杜鹏 苏东明

中国药科大学学报2025,Vol.56Issue(6):747-757,11.
中国药科大学学报2025,Vol.56Issue(6):747-757,11.DOI:10.11665/j.issn.1000-5048.2025051302

Isthmin-1通过上皮-间质转化促进胰腺癌转移侵袭的机制研究

Isthmin-1 drives pancreatic cancer invasion and metastasis through epithelial-mesenchymal transition

张新宇 1徐智超 1王振涛 1陈庆 1秦杜鹏 1苏东明1

作者信息

  • 1. 南京医科大学基础医学院病理系,南京 211166
  • 折叠

摘要

Abstract

To investigate the effect of isthmin-1(ISM1)on the invasion and metastasis of pancreatic cancer and its underlying mechanism,this study analyzed the expression of ISM1 in pancreatic cancer patients and normal pancreatic tissues using The Cancer Genome Atlas(TCGA)database.Western blot was employed to detect differences in ISM1 protein expression between pancreatic cancer cell lines(Aspc1,Bxpc3,PANC1,SW1990)and the pancreatic epithelial cell line(hPNE).Cell models with stable ISM1 overexpression and knockdown were constructed,and changes in cell migration and invasion capabilities were assessed via Transwell invasion assays and wound healing assays.Meanwhile,Western blot was used to detect the expression levels of key markers of epithelial-mesenchymal transition(EMT).Furthermore,TCGA and the Gene Expression Omnibus(GEO)database were utilized to analyze pathways regulated downstream of ISM1 and the mechanisms promoting pancreatic cancer invasion and metastasis.Immunoprecipitation combined with mass spectrometry(IP-MS)was used to screen for vimentin as an ISM1-binding protein,and the interaction between ISM1 and vimentin was verified by immunofluorescence and co-immunoprecipitation(Co-IP).Bxpc3 cells overexpressing ISM1 were treated with the protein synthesis inhibitor cycloheximide(CHX)to detect vimentin protein stability.The results indicate that ISM1 promotes the EMT process by inhibiting vimentin degradation,thereby enhancing the invasion and metastasis of pancreatic cancer.This study provides new experimental evidence for elucidating the mechanism of pancreatic cancer metastasis.

关键词

isthmin-1/胰腺癌/上皮间质转化/肿瘤转移/Transwell实验

Key words

isthmin-1/pancreatic cancer/epithelial-mesenchymal transition(EMT)/tumor metastasis/transwell assay

分类

医药卫生

引用本文复制引用

张新宇,徐智超,王振涛,陈庆,秦杜鹏,苏东明..Isthmin-1通过上皮-间质转化促进胰腺癌转移侵袭的机制研究[J].中国药科大学学报,2025,56(6):747-757,11.

中国药科大学学报

OA北大核心

1000-5048

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