期刊
ARCHIVES OF TOXICOLOGY
卷 89, 期 8, 页码 1371-1381出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-014-1301-z
关键词
Colorectal cancer; BPA; EMT; Proteomic; Tumorigenesis; Migration
类别
资金
- National Natural Science Foundation of China [31101071, 81302317]
- Fundamental Research Funds for the Central Universities (Sun Yat-sen University) [12ykpy09]
- Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation [2011A060901014-007]
- National Basic Research Program of China (973 Program) [2011CB9358003]
- Science and Technology Planning Project of Guangdong Province, China [2012B031500005]
- Seed Collaborative Research Fund from the State Key Laboratory in Marine Pollution [SCRF0003]
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-3 beta-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.
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