title: Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway.
abstract: Lung cancer is one of the leading causes of cancer deaths worldwide. Recent evidences indicated that bisphenol A (BPA), a wide contaminant with endocrine disrupting activity, could enhance the susceptibility of carcinogenesis. Although there are increasing opportunities for lung cells exposure to BPA via inhalation, there is no study concerning the effects of BPA on the development of lung cancer. The present study revealed that BPA less than 10(-4)M had limited effects on the proliferation of lung cancer A549 cells, however, BPA treatment significantly stimulated the in vitro migration and invasion of cells combing with the morphological changes and up regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. G-protein-coupled estrogen receptor (GPER), while not estrogen receptor α/β (ERα/β), mediated the BPA induced up regulation of MMPs. Further, BPA treatment induced rapid activation of ERK1/2 via GPER/EGFR. GPER/ERFR/ERK1/2 mediated the BPA induced upregulation of MMPs and in vitro migration of lung cancer A549 cells. In summary, our data presented here revealed for the first time that BPA can promote the in vitro migration and invasion of lung cancer cells via upregulation of MMPs and GPER/EGFR/ERK1/2 signals, which mediated these effects. This study suggested that more attention should be paid on the BPA and other possible environmental estrogens induced development of lung cancer.
authors.affiliation: Department of Pharmacy, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Kun-Shui
authors.initials: KS
authors.lastname: Zhang
authors.affiliation: Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510310, China.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
authors.forename: Yi-Shen
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Qiu
authors.affiliation: Department of Respiratory Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Zheng
authors.affiliation: Department of Pharmacy, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China. Electronic address: yanghaidisysu@163.com.
authors.forename: Hai-Di
authors.initials: HD
authors.lastname: Yang
authors.affiliation: Guangdong Prevention and Treatment Center for Occupational Diseases, Guangzhou 510310, China.
authors.forename: Cui-Ju
authors.initials: CJ
authors.lastname: Wen
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000096:biosynthesis*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D010636:Phenols / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D066246:ErbB Receptors; D004968:Estrogens, Non-Steroidal; D020782:Matrix Metalloproteinases; D010636:Phenols; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C109584:GPER1 protein, human; C512478:EGFR protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Lung cancer; MMP; Migration