Oncotarget

Research Papers:

Gelsolin suppresses gastric cancer metastasis through inhibition of PKR-p38 signaling

Xiangliang Yuan, Weiwei Wang, Junhua Li, Peiming Zheng, Ping Dong, Lei Chen, Yunlan Zhou, Guohua Xie, Dakang Xu, Yingbin Liu and Lisong Shen _

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Oncotarget. 2016; 7:53459-53470. https://doi.org/10.18632/oncotarget.10557

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Abstract

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

Correspondence to:

Lisong Shen, email: lisongshen@hotmail.com

Keywords: gelsolin, gastric cancer, metastasis, PKR, p38MAPK protein kinase

Received: May 18, 2015    Accepted: July 05, 2016    Published: July 13, 2016

ABSTRACT

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.


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