title: Systems pharmacology of mifepristone (RU486) reveals its 47 hub targets and network: comprehensive analysis and pharmacological focus on FAK-Src-Paxillin complex.
abstract: Mifepristone (RU486), a synthetic steroid compound used as an abortifacient drug, has received considerable attention to its anticancer activity recently. To explore the possibility of using mifepristone as a cancer metastasis chemopreventive, we performed a systems pharmacology analysis of mifepristone-related molecules in the present study. Data were collected by using Natural Language Processing (NLP) and 513 mifepristone-related genes were dug out and classified functionally using a gene ontology (GO) hierarchy, followed by KEGG pathway enrichment analysis. Potential signal pathways and targets involved in cancer were obtained by integrative network analysis. Total thirty-three proteins were involved in focal adhesion-the key signaling pathway associated with cancer metastasis. Molecular and cellular assays further demonstrated that mifepristone had the ability to prevent breast cancer cells from migration and interfere with their adhesion to endothelial cells. Moreover, mifepristone inhibited the expression of focal adhesion kinase (FAK), paxillin, and the formation of FAK/Src/Paxillin complex, which are correlated with cell adhesion and migration. This study set a good example to identify chemotherapeutic potential seamlessly from systems pharmacology to cellular pharmacology, and the revealed hub genes may be the promising targets for cancer metastasis chemoprevention.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Suhong
authors.initials: S
authors.lastname: Yu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Xingtian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Fuzhou General Hospital, Fuzhou 350025, China.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Yan
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Mo
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Guoneng
authors.initials: G
authors.lastname: Cai
authors.affiliation: Rutgers, The State University of New Jersey, New Jersey 08854, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Sinko
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D015735:Mifepristone / Q000633:toxicity*; D051419:Paxillin / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*
chemical_list: D051419:Paxillin; D015735:Mifepristone; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)