Abstract 1925: ZDHHC14, a potential regulator in peritoneal dissemination of scirrhous type gastric cancer, identified by CAST method.

Abstract

Abstract Gastric cancer (GC) is one of the most common malignancies worldwide and is one of the leading causes of cancer related mortality. Among gastric cancer subtypes, scirrhous type GC is highly aggressive and has a worse prognosis because of its diffuse infiltration pattern. Because of such pathological features, early clinical diagnosis of scirrhous gastric carcinoma remains difficult. Moreover, peritoneal dissemination occurs frequently even after radical surgery and is the cause of death in many patients. A potential diagnostic or therapeutic target to identify or to inhibit the mechanism of peritoneal dissemination would be an advantageous in this field and need to be elucidated. Escherichia coli ampicillin secretion trap (CAST) method is a powerful technique to identify novel genes that encode secreted or transmembrane proteins. We previously reported DSC2 (desmocollin 2), identified by this method, as a key regulator of GC with intestinal phenotype, using MKN-1 and MKN-28 GC cell lines. In this study, mRNAs were extracted from HSC-44PE and 44As3 scirrhous GC cell lines to analyze the gene expression profile. HSC-44PE cell line was established from pleural fluid of a patient with scirrhous GC. 44As3, derived from HSC-44PE cells, by isolating a highly disseminated clones with a strong capability of inducing ascites in mouse model. Randomly primed cDNAs ligated with pCAST vector were picked up and sequenced thereafter. Among the candidate genes, ZDHHC14 (zinc finger, DHHC-type containing 14) showed higher expression in 44As3 CAST library than in HSC-44PE library. ZDHHC14 is one of the palmitoyl transferase family members and is supposed to be associated with substrates linked to dissemination cascade in scirrhous type GC. Indirect immunofluorescence microscopic analysis also revealed that ZDHHC14 expression was found mostly in large cells of both cell lines, however, ZDHHC14 staining was more frequently observed in 44As3 than in HSC-44PE. High level of ZDHHC14 expression was observed in 27% of GC samples by qRT-PCR. Cell invasion assay and MTT assay revealed that ZDHHC14 influenced the invasion and growth capacity of GC cells. Identification of the palmitoylated proteins, the substrates of ZDHHC14, remain under investigation. ZDHHC14 identified by CAST method, might contribute in the process of peritoneal dissemination of the gastric cancer cells and it might be a potential therapeutic target for scirrhous type GC. Citation Format: Htoo Zarni Oo, Naoya Sakamoto, Naohiro Uraoka, Katsuhiro Anami, Kazuhiro Sentani, Naohide Oue, Kazuyoshi Yanagihara, Wataru Yasui. ZDHHC14, a potential regulator in peritoneal dissemination of scirrhous type gastric cancer, identified by CAST method. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1925. doi:10.1158/1538-7445.AM2013-1925