1. Academic Validation
  2. FAK/IL-8 axis promotes the proliferation and migration of gastric cancer cells

FAK/IL-8 axis promotes the proliferation and migration of gastric cancer cells

  • Gastric Cancer. 2023 Mar 23. doi: 10.1007/s10120-023-01384-3.
Yuze Ma # 1 Yu Fu # 1 Xiaoli Fan 1 Qiang Ji 1 XiaoJiao Duan 1 Yanfeng Wang 1 Yongmin Zhang 2 Zhigang Wang 1 Huifang Hao 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China.
  • 2 Department of Chemistry and Chemical Engineering, Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China.
  • 3 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China. 111981355@imu.edu.cn.
  • 4 Department of Chemistry and Chemical Engineering, Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China. 111981355@imu.edu.cn.
  • # Contributed equally.
Abstract

Gastric Cancer (GC) is one of the most common malignancies in China and is associated with high mortality. The occurrence and development of gastric Cancer are related to genetic and environmental factors. Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor protein tyrosine kinase that is activated by the extracellular matrix and growth factors. FAK is highly expressed in Cancer and promotes its development by regulating Cancer cell proliferation, migration, and angiogenesis. The expression of IL-8 is increased in many types of malignant tumor cells and is linked to their proliferation, migration, invasion, angiogenesis, and EMT. In this study, we found FAK to be essential for the proliferation, migration, and peritoneal metastasis of gastric Cancer cells. To examine the molecular regulatory mechanisms of FAK in the peritoneal dissemination of gastric Cancer, we performed RNA-seq analysis of MKN-45-FAK-/- and MKN45 cells and demonstrated that IL-8 was downregulated in FAK-deficient cells. Conversely, we confirmed that IL-8 activates FAK activity. We established that IL-8 promotes the proliferation, colony formation, and migration of gastric Cancer cells that are partially mediated by FAK. Thus, we propose that an IL-8-FAK-IL-8 positive feedback loop effects the proliferation and migration of gastric Cancer cells.

Keywords

Focal adhesion kinase; Gastric cancer; Interleukin-8; Migration; Proliferation.

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