title: 6-OH-BDE-47 promotes human lung cancer cells epithelial mesenchymal transition via the AKT/Snail signal pathway.
abstract: Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been detected in the various human tissues. The OH-PBDEs are suggested to be stronger endocrine-disrupting compounds than PBDEs, therefore the toxicological effects of OH-PBDEs had received lots of attention. However, there is no study about the carcinogenic effect of OH-PBDEs and their estrogen potencies on the tumorigenesis and development of cancer. In the present study, we found that 6-hydroxy-2,2',4',4'-tetrabromodiphenyl ether (6-OH-BDE-47), the most abundant OH-PBDE congeners in human serum, promoted the in vitro migration of lung cancer A549 and H358 cells by induction of epithelial to mesenchymal transition (EMT). This was confirmed by that 6-OH-BDE-47 significantly down regulated the expression of epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1) while up regulated the mesenchymal markers vimentin (Vim) and N-cadherin (N-Cad). 6-OH-BDE-47 up regulated the protein while not mRNA levels of Snail, which was the key transcription factor of EMT. Silencing of Snail by use of siRNA attenuated the 6-OH-BDE-47 induced EMT. This suggested that the stabilization of Snail was essential for 6-OH-BDE-47 induced EMT. Further, the treatment of 6-OH-BDE-47 increased the phosphorylation of AKT and ERK in A549 cells. Only PI3K/AKT inhibitor (LY294002), but not ERK inhibitor (PD98059), completely blocked the 6-OH-BDE-47 induced up regulation of Snail and down regulation of E-Cad, suggesting that PI3K/AKT pathway is important for 6-OH-BDE-47-mediated Snail stabilization and EMT in A549 cells. Generally, our results revealed for the first time that 6-OH-BDE-47 promoted the EMT of lung cancer cells via AKT/Snail signals. This suggested that more attention should be paid to the effects of OH-PBDEs on tumorigenesis and development of lung cancer.
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China. Electronic address: qubaolinbeijing@163.com.
authors.forename: Bao-Lin
authors.initials: BL
authors.lastname: Qu
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China.
authors.forename: Bo-Ning
authors.initials: BN
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China.
authors.forename: Le-Hui
authors.initials: LH
authors.lastname: Du
authors.affiliation: Department of Radiation Oncology, PLA General Hospital, Beijing 100853, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: C580599:6-OH-BDE-47; D011075:Polybrominated Biphenyls; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt
keywords: 6-OH-BDE-47; Epithelial to mesenchymal transition; Lung cancer; Snail