Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma

Chia Hung Liu, Tzu Chi Chen, Gar Yang Chau, Yi Hua Jan, Chun Houh Chen, Chun Nan Hsu, Kuan Ting Lin, Yue Li Juang, Pei Jung Lu, Hui Chuan Cheng, Ming Huang Chen, Chia Fen Chang, Yu Shan Ting, Cheng Yan Kao, Michael Hsiao, Chi Ying F. Huang

研究成果: Article同行評審

25 引文 斯高帕斯(Scopus)

摘要

Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKLFLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.

原文English
頁(從 - 到)1335-1349
頁數15
期刊Molecular and Cellular Proteomics
12
發行號5
DOIs
出版狀態Published - 2013 五月

All Science Journal Classification (ASJC) codes

  • 分析化學
  • 生物化學
  • 分子生物學

指紋

深入研究「Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma」主題。共同形成了獨特的指紋。

引用此