KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21

Dai Yuedi; Liu Houbao; Lu Pinxiang; Wang Hui; Tao Min; Zhang Dexiang

doi:10.1016/j.yexcr.2019.111784

KLF2 induces the senescence of pancreatic cancer cells by cooperating with FOXO4 to upregulate p21

Exp Cell Res. 2020 Mar 1;388(1):111784. doi: 10.1016/j.yexcr.2019.111784. Epub 2019 Dec 19.

Authors

Dai Yuedi¹, Liu Houbao², Lu Pinxiang³, Wang Hui⁴, Tao Min⁵, Zhang Dexiang⁶

Affiliations

¹ Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Soochow, 215006, China; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, 200240, China. Electronic address: 20174132209@stu.suda.edu.cn.
² General Surgery Department, Zhongshan Hospital, General Surgery Institute, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China. Electronic address: liu.houbao@zs-hospital.sh.cn.
³ General Surgery Department, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, 200031, China. Electronic address: 13111210052@fudan.edu.cn.
⁴ General Surgery Department, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, 200031, China. Electronic address: Wang.jiwen@zs-hospital.sh.cn.
⁵ Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Soochow, 215006, China. Electronic address: taomin@suda.edu.cn.
⁶ General Surgery Department, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, 200031, China. Electronic address: dexiangzhang12@fudan.edu.cn.

PMID: 31866399
DOI: 10.1016/j.yexcr.2019.111784

Abstract

Pancreatic cancer is one of the most common malignancies in the world. Senescence is frequently observed in the progression of pancreatic cancer. In a previous study, we showed that KLF2 inhibited the growth and migration of pancreatic cancer. However, the mechanisms are not fully understood. In this study, we showed that overexpression of KLF2 induced the senescence of pancreatic cancer cells and inhibited tumorigenesis, and knockdown of KLF2 inhibited senescence and p21 expression. In the molecular mechanism study, KLF2 was found to interact with FOXO4 and cooperated with FOXO4 to induce the expression of p21. Downregulation of p21 and FOXO4 impaired the induction of senescence by KLF2. Overall, this study revealed the functions and mechanisms of KLF2 in senescence and provided a novel explanation for the suppressive roles of KLF2 in pancreatic cancer.

Keywords: FOXO4; KLF2; Pancreatic cancer; Senescence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinogenesis
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
Cell Line
Cells, Cultured
Cellular Senescence*
Cyclin-Dependent Kinase Inhibitor p21 / genetics*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Forkhead Transcription Factors / genetics*
Forkhead Transcription Factors / metabolism
Kruppel-Like Transcription Factors / genetics*
Kruppel-Like Transcription Factors / metabolism
Male
Mice
Mice, Nude
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / metabolism*
Protein Binding
Up-Regulation

Substances

Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor p21
Forkhead Transcription Factors
FoxO4 protein, mouse
Klf2 protein, mouse
Kruppel-Like Transcription Factors