PERK-eIF2α-ERK1/2 axis drives mesenchymal-endothelial transition of cancer-associated fibroblasts in pancreatic cancer

被引：27

作者：

Cai, Wenrun ^{[1
]}

Sun, Xugang ^{[1
]}

Jin, Fanjie ^{[1
]}

Xiao, Di ^{[1
]}

Li, Hui ^{[1
]}

Sun, Huizhi ^{[1
]}

Wang, Yifei ^{[1
]}

Lu, Yang ^{[1
]}

Liu, Jing ^{[1
]}

Huang, Chongbiao ^{[1
]}

Wang, Xiuchao ^{[1
]}

Gao, Song ^{[1
]}

Wang, Hongwei ^{[1
]}

Gao, Chuntao ^{[1
]}

Zhao, Tiansuo ^{[1
]}

Hao, Jihui ^{[1
]}

机构：

[1] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Tianjins Clin Res Ctr Canc, Dept Pancreat Canc,Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China

来源：

CANCER LETTERS | 2021年 / 515卷

基金：

中国国家自然科学基金;

关键词：

PDAC; MEndoT; ER stress; Transdifferentiation; Angiogenesis; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; ANGIOGENESIS; DIFFERENTIATION; HALLMARKS; GROWTH; PERK;

D O I：

10.1016/j.canlet.2021.05.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia, usually driven by cancerassociated fibroblasts (CAFs), influencing patient prognosis. CAFs are a group of plastic cells responsible for tumor growth and metastasis. Fibroblasts have been reported to directly contribute to angiogenesis by undergoing mesenchymal-endothelial transition (MEndoT) after ischemic injury in the heart, brain, and hindlimbs. However, whether CAFs can undergo similar transdifferentiation in the hostile tumor microenvironment and directly contribute to tumor angiogenesis remains unclear. Herein, we provide evidence that CAFs can adopt an endothelial cell-like phenotype and directly contribute to tumor angiogenesis in vitro and in vivo. Furthermore, this program is regulated by the PERK-eIF2 alpha-ERK1/2 axis. Pharmacological inhibition of PERK with GSK2606414 limited the phenotypic transition of CAFs. In conclusion, our results suggest that CAFs contribute to tumor angiogenesis by undergoing the MEndoT, thus representing therapeutic targets for improving PDAC prognosis.

引用

页码：86 / 95

页数：10

共 38 条

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