title: Pharmacoproteomic analysis reveals that metapristone (RU486 metabolite) intervenes E-cadherin and vimentin to realize cancer metastasis chemoprevention.
abstract: Metapristone is the most predominant biological active metabolite of mifepristone, and being developed as a novel cancer metastasis chemopreventive agent by us. Despite its prominent metastasis chemopreventive effect, the underlying mechanism remains elusive. Our study, for the first time, demonstrated that metapristone had the ability to prevent breast cancer cells from migration, invasion, and interfere with their adhesion to endothelial cells. To explore the underlying mechanism of metapristone, we employed the iTRAQ technique to assess the effect of metapristone on MDA-MB-231 cells. In total, 5,145 proteins were identified, of which, 311 proteins showed significant differences in metapristone-treated cells compared to the control group (P-value < 0.05). Bioinformatic analysis showed many differentially expressed proteins (DEPs) functionally associated with post-translational modification, chaperones, translation, transcription, replication, signal transduction, etc. Importantly, many of the DEPs, such as E-cadherin, vimentin, TGF-β receptor I/II, smad2/3, β-catenin, caveolin, and dystroglycan were associated with TGF-β and Wnt signaling pathways, which were also linked to epithelial-to-mesenchymal transition (EMT) process. Further validation of the epithelial marker "E-caderin" and mesenchymal marker "vimetin" were carried out using immunoblot and immunofluorescence. These results have revealed a novel mechanism that metapristone-mediated metastasis chemoprevention is through intervening the EMT-related signaling pathways.
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: 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: 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: Sudang
authors.initials: S
authors.lastname: He
authors.affiliation: Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou, 350002, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou Fujian, 350108, China.
authors.forename: Chongtao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Internal Oncology Laboratory, Fujian Provincial Key Laboratory of Translational Medicine Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, 350002, China.
authors.forename: Chuanzhong
authors.initials: C
authors.lastname: Huang
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: Zhongping
authors.initials: Z
authors.lastname: Tian
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: D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D063990:Gene Ontology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007553:Isotope Labeling; D055442:Metabolome / Q000187:drug effects; D015735:Mifepristone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D009363:Neoplasm Proteins; D014746:Vimentin; D015735:Mifepristone; C000592521:metapristone