title: Pentabromophenol suppresses TGF-β signaling by accelerating degradation of type II TGF-β receptors via caveolae-mediated endocytosis.
abstract: Pentabromophenol (PBP), a brominated flame retardant (BFR), is widely used in various consumer products. BFRs exert adverse health effects such as neurotoxic and endocrine-disrupting effects. In this study, we found that PBP suppressed TGF-β response by accelerating the turnover rate of TGF-β receptors. PBP suppressed TGF-β-mediated cell migration, PAI-1 promoter-driven reporter gene activation, and Smad2/3 phosphorylation in various cell types. Furthermore, PBP abolished TGF-β-mediated repression of E-cadherin expression, in addition to the induction of vimentin expression and N-cadherin and fibronectin upregulation, thus blocking TGF-β-induced epithelial-mesenchymal transition in A549 and NMuMG cells. However, this inhibition was not observed with other congeners such as tribromophenol and triiodophenol. TGF-β superfamily members play key roles in regulating various biological processes including cell proliferation and migration as well as cancer development and progression. The results of this in vitro study provide a basis for studies on the detailed relationship between PBP and modulation of TGF-β signalling. Because PBP is similar to other BFRs such as polybrominated diphenyl ethers (PBDEs), additional laboratory and mechanistic studies should be performed to examine BFRs as potential risk factors for tumorigenesis and other TGF-β-related diseases.
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan, ROC.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Kao
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.
authors.forename: Chih-Ling
authors.initials: CL
authors.lastname: Chung
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D021941:Caveolae / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D004705:Endocytosis; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010636:Phenols / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010636:Phenols; D018125:Receptors, Transforming Growth Factor beta; C098189:pentabromophenol; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II