2. Academic Validation
  3. The kinase activity of integrin-linked kinase regulates cellular senescence in gastric cancer

The kinase activity of integrin-linked kinase regulates cellular senescence in gastric cancer

  • Cell Death Dis. 2022 Jul 1;13(7):577. doi: 10.1038/s41419-022-05020-3.
Chengbo Ji  # 1 2,  Mili Zhang  # 1,  Junjie Hu  # 3,  Can Cao 1,  Qisheng Gu 4,  Youdong Liu 1,  Xu Li 1,  Duogang Xu 1,  Le Ying 5 6,  Yuqin Yang 7,  Hugh Gao 6,  Jikun Li 8,  Liang Yu 9
Affiliations

Affiliations

  • 1 Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 2 Department of General Surgery, Zhongshan Hospital, General Surgery Research Institute, Fudan University, Shanghai, 200032, China.
  • 3 Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 4 Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 5 Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
  • 6 Department of Molecular Translational Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, 3800, Australia.
  • 7 Department of Laboratory Animal Centre, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 8 Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. lijikunphd@163.com.
  • 9 Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China. Liang.yu@shgh.cn.
  • # Contributed equally.
PMID: 35778385 DOI: 10.1038/s41419-022-05020-3
Abstract

The activity of integrin-linked kinase (ILK) in cancerous cells is often oncogenic and associated with malignant properties, such as uncontrolled cell cycle progression and evasion from senescence. However, the role of ILK in cellular senescence in gastric Cancer (GC) has not been previously examined. We generated single-cell clones of ILK knock-out using CRISPR-Cas9 in human GC lines with mesenchymal or epithelial histology. Cells with no residual ILK expression exhibited strong cellular senescence with diminished clathrin-mediated endocytosis, Surprisingly, ILK loss-induced cellular senescence appeared to be independent of its function in Integrin signaling. The low dose of CPD22, a small molecule inhibitor of ILK activity-induced senescence in three GC cell lines with different histologies. Furthermore, senescent cells with ILK depletion transfected with N-terminal truncated ILK mutant remaining catalytic domains displayed the reduction of senescent phenotypes. RNA Sequencing and cytokine array results revealed the enrichment of multiple pro-inflammatory signaling pathways in GC lines in the absence of ILK. Our study identified the important role and the potential mechanism of ILK in the cellular senescence of cancerous epithelial cells. The inhibition of ILK activity using small molecule compounds could have a pro-senescent effect as a therapeutic option for GC.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z