Gastric cancer cell line proteome and phosphoproteome analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Jun Adachi
PROVIDER: PXD050832 | JPOST Repository | Wed Sep 18 00:00:00 BST 2024
REPOSITORIES: jPOST
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Project description:Regions of recurrent genomic amplification and deletion are frequently observed in primary gastric cancers (GC). However, identifying specific oncogenes and tumor suppressor genes within these regions can be challenging, as they often cover tens to hundreds of genes. Here, we combined high-resolution array-based comparative genomic hybridization (aCGH) with gene expression profiling to target genes lying within focal high-level amplifications in GC cell lines, and identified RAB23 as an amplified and overexpressed Chr 6p11p12 gene in Hs746T cells. High RAB23 protein expression was also observed in some lines lacking RAB23 amplification, suggesting additional mechanisms besides gene amplification for up-regulating RAB23. siRNA silencing of RAB23 reduced the invasive potential of both amplified and nonamplified GC cell lines. RAB23 gene amplifications were observed in 13% of primary gastric carcinomas. In two independent patient cohorts, RAB23 transcript and protein expression was significantly associated with diffuse-type gastric cancer (dGC) compared to intestinal-type gastric cancer (iGC), providing further evidence that dGC and iGC likely represent two molecularly distinct tumor types. Our study demonstrates that investigating focal chromosomal amplifications by combining highresolution aCGH with expression profiling is a powerful general strategy for identifying novel cancer genes in recurrent regions of chromosomal aberration. Keywords: gastric cancer cell lines, comparative genomic hybridization, gene expression profiling Affy 100K SNP profiling and 32K BAC Array profiling for 7 Gastric Cancer Cell Lines
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Project description:Gastric cancer is one of the world common causes of cancer death. Many people have suffered, but yet therapeutic methods found. May studies have showedthat Tanshinone IIA, a diterpenequinone, which extracted from the traditional herbal medicine Danshen (Salvia miltiorrhiza),has potential against many kind of cancer types. Our previous studies have demonstrated TIIA can kill gastric cancer AGS cells, but the response signalling is still unclear. Therefore, we used the time-dependent phosphoproteomic approach to reveal the regulatory effects of TIIA in AGS cells. Our results showed that a total of 1092 phosphoprotiens and 3332 phosphopeptides were identified in 3615 phosphorylation sites and 349 phosphosites corresponding to 220 phosphorylated proteins were significantly regulated. Furthermore, by using networkand functionalenrichmentanalyses, we found that TIIA regulated several cellular processesingastric cancer cells, such astranscription mRNA processing, DNA damage and protein unfolding response. Finally, we further validated that TIIA caused protein unfolding response and DNA damage via inducing ROS production. These findings not only uncover the molecular mechanisms mediated by TIIA but also contribute to the development of gastric cancer therapy.
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