Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets
文献类型：期刊论文
| 作者 | Lu, Junyan2; Zeng, Hanlin2; Liang, Zhongjie1; Chen, Limin2; Zhang, Liyi2; Zhang, Hao2; Liu, Hong2 ; Jiang, Hualiang2; Shen, Bairong1; Huang, Ming2
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| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2015-10-08 |
| 卷号 | 5 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep14739 |
| 文献子类 | Article |
| 英文摘要 | The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a pro-tumor inflammatory microenvironment. Furthermore, in silico mutation studies and experimental validations led to a novel finding that concurrently targeting ceramide and PI3K/AKT pathway by chemical probes or marketed drugs achieves synergistic anti-cancer effects. Overall, our network model can guide further mechanistic studies on CAC and provide new insights into the design of combinatorial cancer therapies in a rational manner. |
| WOS关键词 | SIGNAL-TRANSDUCTION NETWORKS ; INFLAMMATORY-BOWEL-DISEASE ; HUMAN COLORECTAL-CARCINOMA ; RAS GENE-MUTATIONS ; TUMOR PROGRESSION ; REGULATORY NETWORKS ; MEDIATED APOPTOSIS ; EPITHELIAL-CELLS ; DENDRITIC CELLS ; BOOLEAN MODELS |
| 资助项目 | Hi-Tech Research and Development Program of China[2012AA020302] ; Ministry of Science and Technology of China[2015CB910304] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81302700] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000362414300001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276366]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Huang, Ming |
| 作者单位 | 1.Soochow Univ, Ctr Syst Biol, Suzhou, Jiangsu, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 3.Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA |
| 推荐引用方式 GB/T 7714 | Lu, Junyan,Zeng, Hanlin,Liang, Zhongjie,et al. Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets[J]. SCIENTIFIC REPORTS,2015,5. |
| APA | Lu, Junyan.,Zeng, Hanlin.,Liang, Zhongjie.,Chen, Limin.,Zhang, Liyi.,...&Luo, Cheng.(2015).Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets.SCIENTIFIC REPORTS,5. |
| MLA | Lu, Junyan,et al."Network modelling reveals the mechanism underlying colitis-associated colon cancer and identifies novel combinatorial anti-cancer targets".SCIENTIFIC REPORTS 5(2015). |
入库方式： OAI收割
来源：上海药物研究所
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