Project description:single-cell Gene expression signatures in gastric tissues of sstr2 knockout and wild type mice using Chromium’s 10x single-cell RNA-seq platform
Project description:Gastric cancer (GC) is one of the most common malignant cancers in the world. c-Myc, a well-known oncogene, is commonly amplified in many cancers, including gastric cancer. However, it is still not completely understood how c-Myc functions in GC. Here, we generated a stomach-specific c-Myc knock-in mouse model to investigate its role in GC. We found that overexpression of c-Myc in Atp4b+ gastric parietal cells could induce intestinal-type gastric cancer in mice. Mechanistically, c-Myc promoted tumorigenesis via the AKT/mTOR pathway. Furthermore, AKT inhibitor (MK-2206) or mTOR inhibitor (Rapamycin) inhibited the proliferation of c-Myc overexpressing gastric cancer cell lines. Thus, our findings highlight that gastric cancer can be induced by c-Myc overexpression through activation of the AKT/mTOR pathway.
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