Open AccessHigh KRT 8 expression promotes tumor progression and metastasis of gastric cancer
Author(s) -
Fang Jian,
Wang Hao,
Liu Yun,
Ding Fangfang,
Ni Ying,
Shao Shihe
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13120
Subject(s) - metastasis , cancer , downregulation and upregulation , epithelial–mesenchymal transition , medicine , cancer research , biology , immunology , gene , biochemistry
Keratin8 ( KRT 8) is the major component of the intermediate filament cytoskeleton and predominantly expressed in simple epithelial tissues. Aberrant expression of KRT 8 is associated with multiple tumor progression and metastasis. However, the role of KRT 8 in gastric cancer ( GC ) remains unclear. In this study, KRT 8 expression was investigated and it was found to be upregulated along with human GC progression and metastasis at both mRNA and protein levels in human gastric cancer tissues. In addition, KRT 8 overexpression enhanced the proliferation and migration of human gastric cancer cells, whereas the knock‐down of KRT 8 by si RNA only inhibited migration of human gastric cancer cells. Integrinβ1‐ FAK ‐induced epithelial‐mesenchymal‐transition ( EMT ) only existed in the high KRT 8 cells. Furthermore, KRT 8 overexpression led to increase in p‐smad2/3 levels and TGF β dependent signaling events. KRT 8 expression in GC was related to tumor clinical stage and worse survival. Kaplan–Meier analysis proved that KRT 8 was associated with overall survival of patients with GC that patients with high KRT 8 expression tend to have unfavorable outcome. Moreover, Cox's proportional hazards analysis showed that high KRT 8 expression was a prognostic marker of poor outcome. These results provided that KRT 8 expression may therefore be a biomarker or potential therapeutic target to identify patients with worse survival.