KRT7 promotes pancreatic cancer metastasis by remodeling the extracellular matrix niche through FGF2-fibroblast crosstalk

被引:0
作者
Jiang, Yuting [1 ,2 ,4 ]
Liao, Chengyu [1 ,3 ,4 ]
Lai, Jianlin [1 ,3 ,4 ]
Peng, Yunyi [1 ]
Chen, Qilin [1 ]
Zheng, Xiaoling [1 ,2 ,4 ]
机构
[1] Fujian Med Univ, Shengli Clin Med Coll, Fuzhou 350001, Peoples R China
[2] Fujian Prov Hosp, Dept Digest Endoscopy, 134 East St, Fuzhou 350001, Peoples R China
[3] Fujian Prov Hosp, Dept Hepatobiliary Pancreat Surg, 134 East St, Fuzhou 350001, Peoples R China
[4] Fuzhou Univ, Affiliated Prov Hosp, Fuzhou 350001, Peoples R China
来源
SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期
基金
中国国家自然科学基金;
关键词
Pancreatic ductal adenocarcinoma; Metastasis; Extracellular matrix; Cancer-associated fibroblasts; Fibroblasts; CATENIN;
D O I
10.1038/s41598-024-84129-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with a dismal prognosis due to distant metastasis. Through an analysis of large RNA sequencing and proteomics datasets, we found that high KRT7 expression in PDAC patients was correlated with liver metastasis and poor survival. A functional investigation revealed that the overexpression of KRT7 promoted liver metastasis but did not affect tumor cell proliferation in vivo or in vitro. Analysis of scRNA-Seq data from 24 PDAC samples revealed a negative correlation between KRT7 expression in PDAC cells and cancer-associated fibroblast (CAF) infiltration, and this was further confirmed in orthotopic tumor model mice injected with KRT7-overexpressing PDAC cells, which led the development of to a prometastatic niche with reduced ECM deposition. Mechanistically, KRT7 in PDAC cells promoted the secretion of FGF2, which inhibited CAF proliferation and ECM-related gene transcription through the Wnt/beta-catenin pathway. Moreover, targeting FGF2 decreased liver metastasis in vivo. Our study revealed that KRT7 promotes PDAC liver metastasis by remodeling the extracellular matrix niche through FGF2-fibroblast crosstalk and provides a promising strategy for preventing PDAC liver metastasis.
引用
收藏
页数:14
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