FAK/IL-8 axis promotes the proliferation and migration of gastric cancer cells.
Yuze MaYu FuXiaoli FanQiang JiXiaoJiao DuanYanfeng WangYongmin ZhangZhigang WangHuifang HaoPublished in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (2023)
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.
Keyphrases
- cell migration
- tyrosine kinase
- rna seq
- extracellular matrix
- cell proliferation
- induced apoptosis
- signaling pathway
- papillary thyroid
- risk assessment
- squamous cell carcinoma
- endothelial cells
- epidermal growth factor receptor
- type diabetes
- poor prognosis
- oxidative stress
- cardiovascular disease
- genome wide
- high resolution
- lymph node metastasis
- coronary artery disease
- small molecule
- cell death
- staphylococcus aureus
- pseudomonas aeruginosa
- simultaneous determination
- childhood cancer
- wound healing
- protein kinase
- tandem mass spectrometry
- endoplasmic reticulum stress
- mass spectrometry