Downregulation of CYRI-B promotes migration, invasion and EMT by activating the Rac1-STAT3 pathway in gastric cancer

Background: CYRI-B plays key roles in regulating cell motility in nontumor cells. However, the role and function of CYRI-B have rarely been studied in cancer cells, including gastric cancer. The purpose of this study was to investigate the clinical significance, biological function and underlying molecular mechanism of CYRI-B in gastric cancer. Method: CYRI-B protein levels were detected by immunohistochemistry (IHC) and western blotting (WB). Gastric cancer cells and organoid models were evaluated to explore the correlation of CYRI-B with collagen type I. The function of CYRI-B in proliferation, migration, invasion in gastric cancer was evaluated by in vitro and in vivo experiments. Result: CYRI-B protein levels were downregulated in gastric cancer. Low expression of CYRI-B was related to later tumor stage and poorer prognosis. CYRI-B expression was reduced when cells were cultured in collagen type I, which was mediated by collagen receptor DDR1. Knockdown of CYRI-B promoted migration, invasion and EMT in vivo and in vitro. Mechanistically, knockdown of CYRI-B activated the Rac1-STAT3 pathway. Conclusion: Our findings showed that CYRI-B plays an important role in the tumor microenvironment, and is associated with malignant characteristics acquired by gastric cancer. This study may provide new targets for future therapeutic interventions for tumor metastasis.

Automated summary

This study investigated the clinical significance, biological function, and molecular mechanism of CYRI-B in gastric cancer. CYRI-B protein levels were found to be downregulated in gastric cancer, and low expression was associated with later tumor stage and poorer prognosis. The study also revealed that CYRI-B expression was regulated by collagen type I and activation of the Rac1-STAT3 pathway. These findings suggest that CYRI-B is important in the tumor microenvironment and may provide new targets for metastasis treatment.