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Archives of Toxicology

, Volume 89, Issue 8, pp 1371–1381 | Cite as

Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions

Genotoxicity and Carcinogenicity

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.

Keywords

Colorectal cancer BPA EMT Proteomic Tumorigenesis Migration 

Abbreviations

BPA

Bisphenol A

CRC

Colorectal cancer

DMSO

Dimethyl sulfoxide

E2

Estradiol

E-Cad

E-cadherin

EDCs

Endocrine disruptor chemicals

EMT

Epithelial to mesenchymal transitions

ERR

Estrogen-related receptor

ERα/β

Estrogen receptor α/β

FBS

Fetal bovine serum

FN

Fibronectin

GPER

G-protein-coupled estrogen receptor

hsp27

Heat-shock protein 27

N-Cad

N-cadherin

Vim

Vimentin

ZO-1

Zona occludin-1

Notes

Acknowledgments

This research was supported by the National Natural Science Foundation of China (Grant Nos. 31101071 and 81302317), the Fundamental Research Funds for the Central Universities (Sun Yat-sen University) (No. 12ykpy09), the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation (No. 2011A060901014-007), the National Basic Research Program of China (973 Program, No. 2011CB9358003), the Science and Technology Planning Project of Guangdong Province, China (No. 2012B031500005), and the Seed Collaborative Research Fund from the State Key Laboratory in Marine Pollution (SCRF0003).

Supplementary material

204_2014_1301_MOESM1_ESM.doc (1.1 mb)
Supplementary material 1 (DOC 1124 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Pharmacy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina
  2. 2.Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouChina
  3. 3.Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Institute of Human Virology, Key Laboratory of Tropical Disease Control (Ministry of Education)Sun Yat-sen UniversityGuangzhouChina
  4. 4.Cancer Research Institute and Cancer HospitalGuangzhou Medical UniversityGuangzhouChina
  5. 5.Department of Pharmacy, Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina
  6. 6.Department of Veterinary Biomedical Sciences, Toxicological CenterUniversity of SaskatchewanSaskatoonCanada

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