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, Lisong Shen

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)53459-53470
Number of pages12
JournalOncotarget
Volume7
Issue number33
DOIs
Publication statusPublished - 13 Jul 2016

Keywords

  • Gastric cancer
  • Gelsolin
  • Metastasis
  • p38MAPK protein kinase
  • PKR

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