Oncotarget

Research Papers:

Perfluorooctanoic acid induces human Ishikawa endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling

Zhinan Ma, Xiaoqiu Liu, Fujun Li, Yixong Wang, Yang Xu, Mei Zhang, Xiaoqian Zhang, Xiaoyan Ying and Xuesen Zhang _

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Oncotarget. 2016; 7:66558-66568. https://doi.org/10.18632/oncotarget.11684

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Abstract

Zhinan Ma1,2,3,*, Xiaoqiu Liu4,5,*, Fujun Li3, Yixong Wang2, Yang Xu2, Mei Zhang3, Xiaoqian Zhang3, Xiaoyan Ying1 and Xuesen Zhang3

1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

2 Department of Obstetrics and Gynecology, Yangzhou Maternal and Child Health Hospital, Yangzhou University, Yangzhou, China

3 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

4 Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, China

5 Department of Microbiology, Nanjing Medical University, Nanjing, China

* These authors have contributed equally to this work

Correspondence to:

Xuesen Zhang , email:

Xiaoyan Ying , email:

Keywords: endometrial carcinoma, PFOA, migration and invasion, tumorigenesis, ERK/mTOR

Received: May 08, 2016 Accepted: August 25, 2016 Published:August 29, 2016

Abstract

Perfluorooctanoic acid (PFOA) is a common environmental pollutant that has been associated with various diseases, including cancer. We explored the molecular mechanisms underlying PFOA-induced endometrial cancer cell invasion and migration. PFOA treatment enhanced migration and invasion by human Ishikawa endometrial cancer cells, which correlated with decreased E-cadherin expression, a marker of epithelial-mesenchymal transition. PFOA also induced activation of ERK1/2/mTOR signaling. Treatment with rapamycin, an mTOR inhibitor, antagonized the effects of PFOA and reversed the effects of PFOA activation in a xenograft mouse model of endometrial cancer. Consistent with these results, pre-treatment with rapamycin abolished PFOA-induced down-regulation of E-cadherin expression. These results indicate that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling.


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