title: Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions.
abstract: More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3β-mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT.
authors.affiliation: Department of Pharmacy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China, chenzhuojia86@163.com.
authors.forename: Zhuo-Jia
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Kun-Shui
authors.initials: KS
authors.lastname: Zhang
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Huang
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Huan-Liang
authors.initials: HL
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D020543:Proteome / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D009363:Neoplasm Proteins; D010636:Phenols; D020543:Proteome; C006780:bisphenol A; D000098826:Bisphenol A Compounds