IMR Press / FBE / Volume 5 / Issue 2 / DOI: 10.2741/E639

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Effect of genomic instability and mutations on the signaling pathways in colon cancer cells

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1 Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China
2 Departments of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA
3 Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

*Author to whom correspondence should be addressed.

Front. Biosci. (Elite Ed) 2013, 5(2), 574–582; https://doi.org/10.2741/E639
Published: 1 January 2013
Abstract

Microsatellite instability (MSI) is present in about 15% of colorectal cancers and plays critical roles in the development and progression of these cancers. The goal of this study is to determine the global effect of microsatellite instability on the signaling pathways and network in colon cancer cells. We profiled the expression and phosphorylation of 110 proteins in six colon cancer cell lines by using Protein Pathway Array. The pathways and network constituted by these proteins were identified by using Ingenuity Pathway Analysis. Our results showed that 25 proteins and phosphoproteins change more than 1.5-fold between MSI and microsatellite stable (MSS) cells. Sixteen major pathways were affected in MSI cells, including p53 and 14-3-3β pathways, with p53 and HGF being the most important 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 tumorigenesis of MSI colorectal cancer.

Keywords
Microsatellite instability
K-RAS mutation
Protein pathway array
Multiplex immunoblot
Signaling network
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