title: Gelsolin suppresses gastric cancer metastasis through inhibition of PKR-p38 signaling.
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.
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Peiming
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Department of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yunlan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xie
authors.affiliation: MIMR-PHI Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia.|Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, Zhejiang 311121, China.
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Lisong
authors.initials: L
authors.lastname: Shen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018260:Gelsolin / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D019892:eIF-2 Kinase / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018260:Gelsolin; C000602769:EIF2AK2 protein, human; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: PKR; gastric cancer; gelsolin; metastasis; p38MAPK protein kinase