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

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 activ...

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Bibliographic Details
Published in:Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2023-07, Vol.26 (4), p.528-541
Main Authors: Ma, Yuze, Fu, Yu, Fan, Xiaoli, Ji, Qiang, Duan, XiaoJiao, Wang, Yanfeng, Zhang, Yongmin, Wang, Zhigang, Hao, Huifang
Format: Article
Language:English
Subjects:
Abdominal Surgery
Angiogenesis
Cancer Research
Cancer therapies
Cell migration
Cell proliferation
Cytokines
Environmental factors
Extracellular matrix
Focal adhesion kinase
Gastric cancer
Gastroenterology
Gene expression
Growth factors
Health risks
Interleukin 8
Kinases
Malignancy
Medicine
Medicine & Public Health
Metastases
Metastasis
Oncology
Original Article
Peritoneum
Protein-tyrosine kinase
Surgical Oncology
Tumor cells
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Summary: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.
ISSN:1436-3291
1436-3305
DOI:10.1007/s10120-023-01384-3