4.6 Article

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

Journal

EXPERIMENTAL CELL RESEARCH
Volume 388, Issue 1, Pages -

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.111784

Keywords

Pancreatic cancer; Senescence; KLF2; FOXO4

Funding

  1. Shanghai Municipal Health and Family Planning Health Commission [201840036]
  2. JianFeng Project of Shanghai Xuhui Commission of Health and Family Planning [SHXH201703]

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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.

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