title: Overexpression of ZDHHC14 promotes migration and invasion of scirrhous type gastric cancer.
abstract: Scirrhous type gastric cancer is highly aggressive and has a poorer prognosis than many other types of gastric carcinoma, due to its characteristic rapid cancer cell infiltration and proliferation, extensive stromal fibrosis, and frequent peritoneal dissemination. The aim of the present study was to identify novel prognostic markers or therapeutic targets for scirrhous type gastric cancer. We reviewed a list of genes with upregulated expression in scirrhous type gastric cancer and compared their expression with that in normal stomach from our previous Escherichia coli (E. coli) ampicillin secretion-trap (CAST) analysis. We focused on the ZDHHC14 gene, which encodes zinc finger, DHHC-type containing 14 protein. qRT-PCR analysis of ZDHHC14 in 41 gastric cancer cases revealed that compared to mRNA levels in normal non-neoplastic gastric mucosa, ZDHHC14 mRNA was overexpressed in 27% of gastric cancer tissue samples. The overexpression of ZDHHC14 was significantly associated with depth of tumor invasion, undifferentiated histology and scirrhous pattern. The invasiveness of ZDHHC14-knockdown HSC-44PE and 44As3 gastric cancer cells was decreased in comparison with that of the negative control siRNA-transfected cells, together with downregulation of MMP-17 mRNA. Integrins α5 and β1 were also downregulated in ZDHHC14-knockdown 44As3 cells. Forced expression of ZDHHC14 activated gastric cancer cell migration and invasion in vitro. These results indicate that ZDHHC14 is involved in tumor progression in patients with scirrhous type gastric cancer.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Htoo Zarni
authors.initials: HZ
authors.lastname: Oo
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Anami
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Uraoka
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, Yokohama 232-0024, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Translational Research, Exploratory Oncology and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8551, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D002293:Adenocarcinoma, Scirrhous / Q000235:genetics / Q000473:pathology*; D000368:Aged; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D000217:Acyltransferases; C557245:ZDHHC14 protein, human