Gelsolin suppresses gastric cancer metastasis through inhibition of PKR-p38 signaling
Metrics: PDF 1205 views | HTML 1904 views | ?
Xiangliang Yuan1,*, Weiwei Wang1,*, Junhua Li1,*, Peiming Zheng1, Ping Dong2, Lei Chen2, Yunlan Zhou1, Guohua Xie1, Dakang Xu3,4, Yingbin Liu2, Lisong Shen1
1Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
2Department of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
3MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia
4Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 311121, China
*These authors have contributed equally to this work
Lisong Shen, email: email@example.com
Keywords: gelsolin, gastric cancer, metastasis, PKR, p38MAPK protein kinase
Received: May 18, 2015 Accepted: July 05, 2016 Published: July 13, 2016
The biological function of gelsolin in gastric cancer and its mechanism remained undefined. Here, we demonstrated that gelsolin was down-regulated in human gastric cancer tissues, and lower tumorous gelsolin significantly correlated with gastric cancer metastasis. Functionally, gelsolin suppressed the migration of gastric cancer cells in vitro and inhibited lung metastasis in vivo. In mechanism, gelsolin decreased epithelial–mesenchymal transition (EMT) inducing cytoskeleton remolding through inhibition of p38 signaling to suppress the migration of gastric cancer cell. Moreover, gelsolin bound to and decreased the phosphorylation of PKR, and then inhibited p38 signaling pathway. Finally, similar to the gastric cancer cell lines, PKR-p38 signaling pathway proteins tend to be activated and correlated with low expression of gelsolin in clinical gastric cancer tissues. Altogether, these results highlight the importance of gelsolin in suppression of gastric cancer metastasis through inhibition of PKR-p38 signaling pathway.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.