ジャーナル・オブ・オンコロジー・トランスレーショナル・リサーチ

Effect of Genomic Instability and Mutations on the Signalling Pathways in Colon Cancer Cells

Abstract

Miao Cui, Fei Ye, Kaijun Huang, Liang , Zhiqing , Yuan , Yulan , Bo Jiang and David Zhang

Colorectal cancer (CRC) is the third most common cancer diagnosed in the United States and the second leading cause of cancer death. Microsatellite instability (MSI) is present in about 15% of colorectal cancers and plays critical roles in the development and progression of these cancers. Several clinical studies showed that MSI colon cancer has a more favorable prognosis and is less prone to lymph node and distance metastasis. Furthermore, the MSI phenotype may also are expecting the response to treatment with 5-fluorouracil (5-FU) and irinotecan. Recent gene expression research discovered alteration of the apoptotic and immune response pathways in MSI cells. However, the role of these pathways inside the carcinogenesis of CRC and the interaction of those protein biomarkers in MSI CRC cells stay to be determined. The goal of this have a look at is to decide the global effect of microsatellite instability on the signalling pathways and network in colon cancer cells to find out the protein biomarker. We profiled the expression and phosphorylation of one hundred ten proteins in six colon most cancers mobile lines by means of using Protein Pathway Array. The pathways and network constituted by using these proteins had been identified by means of using Ingenuity Pathway Analysis. Our outcomes showed that 25 proteins and phosphoproteins change more than 1.5-fold among MSI and microsatellite stable (MSS) cells. Sixteen major pathways have been affected in MSI cells, along with p53 and 14-3-3β pathways, with p53 and HGF being the most essential pathways. Finally, although the EGFR/K-RAS/MEK pathway was not affected in MSI cells, collateral pathways such as the p70S6K and p90RSK pathways were activated in MSI cells. Thus, suppression of the p53 pathway and activation of the HGF pathway in MSI cells may be critical in the tumorgenesis of MSI colorectal cancer.