An integrative approach for the large-scale identification of human genome kinases regulating cancer metastasis |
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Authors: | Hanshuo Zhang Po-Yen Wu Ming Ma Yanzhen Ye Yang Hao Junyu Yang Shenyi Yin Changhong Sun John H. Phan May D. Wang Jianzhong Jeff Xi |
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Affiliation: | 1. Biomedical Engineering Department, College of Engineering;2. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, P. R. China;3. School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA;4. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA;5. The Winship Cancer Institute, Emory University, The Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA |
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Abstract: | Kinases become one of important groups of drug targets. To identify more kinases being potential for cancer therapy, we developed an integrative approach for the large-scale screen of functional genes capable of regulating the main traits of cancer metastasis. We first employed self-assembled cell microarray to screen functional genes that regulate cancer cell migration using a human genome kinase siRNA library. We identified 81 genes capable of significantly regulating cancer cell migration. Following with invasion assays and bio-informatics analysis, we discovered that 16 genes with differentially expression in cancer samples can regulate both cell migration and invasion, among which 10 genes have been well known to play critical roles in the cancer development. The remaining 6 genes were experimentally validated to have the capacities of regulating cell proliferation, apoptosis and anoikis activities besides cell motility. Together, these findings provide a new insight into the therapeutic use of human kinases.From the Clinical EditorThis team of authors have utilized a self-assembled cell microarray to screen genes that regulate cancer cell migration using a human genome siRNA library of kinases. They validated previously known genes and identified novel ones that may serve as therapeutic targets. |
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