title: High KRT8 expression promotes tumor progression and metastasis of gastric cancer.
abstract: Keratin8 (KRT8) is the major component of the intermediate filament cytoskeleton and predominantly expressed in simple epithelial tissues. Aberrant expression of KRT8 is associated with multiple tumor progression and metastasis. However, the role of KRT8 in gastric cancer (GC) remains unclear. In this study, KRT8 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, KRT8 overexpression enhanced the proliferation and migration of human gastric cancer cells, whereas the knock-down of KRT8 by siRNA only inhibited migration of human gastric cancer cells. Integrinβ1-FAK-induced epithelial-mesenchymal-transition (EMT) only existed in the high KRT8 cells. Furthermore, KRT8 overexpression led to increase in p-smad2/3 levels and TGFβ dependent signaling events. KRT8 expression in GC was related to tumor clinical stage and worse survival. Kaplan-Meier analysis proved that KRT8 was associated with overall survival of patients with GC that patients with high KRT8 expression tend to have unfavorable outcome. Moreover, Cox's proportional hazards analysis showed that high KRT8 expression was a prognostic marker of poor outcome. These results provided that KRT8 expression may therefore be a biomarker or potential therapeutic target to identify patients with worse survival.
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fang
authors.affiliation: Second People's Hospital of Wuxi, Wuxi, China.|Nanjing Medical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Ding
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ni
authors.affiliation: School of Medicine, Jiangsu University, Jiangsu, China.
authors.forename: Shihe
authors.initials: S
authors.lastname: Shao
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D053533:Keratin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D034741:RNA, Small Interfering; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
chemical_list: D019012:Integrin beta1; C426203:KRT8 protein, human; D053533:Keratin-8; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Gastric cancer; Keratin; Keratin8; metastasis; survival