Abstract

Abstract Multiple dys-regulated cell signaling pathways and extensive cross-talks, which can be depicted via protein-protein interactions (PPIs), among individual signaling pathways, characterize cancer development and progression. However, systematic analysis of the cross-talk events from distinct pathways via PPIs remains fragmentary, and the reliability of PPI datasets, particularly at the cellular level, remains to be vigorously examined. Here, we first build the cross-talk pathway map of heptocellular carcinoma (HCC) through overexpression patterns in HCC among 23 pathways. By detecting endogenous PPIs in two HCC cell lines, Huh7 (low invasive cells) and Mahlavu (high invasive cells), we validate 50 PPI events within pathway and 19 PPI-mediated cross-talk events among 23 pathways in HCC. Not surprisingly, many distinct PPIs are present between Huh7 and Mahlavu, providing the opportunity to characterize tumor invasion. By analyzing topology of cross-talk PPI network, CRKL has a pivotal role in cross-talk pathway. This initial attempt to map the cross-talk pathways in HCC may represent the first step in deciphering hepatocarcinogenesis at the systems level and might reveal a novel strategy for HCC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4929. doi:10.1158/1538-7445.AM2011-4929

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