Oncotarget

Research Papers:

Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation

Zhaoming Zhong, Zedong Hu, Yue Jiang, Ruimei Sun, Xue Chen, Hongying Chu, Musheng Zeng _ and Chuanzheng Sun

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Oncotarget. 2016; 7:59652-59663. https://doi.org/10.18632/oncotarget.10831

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Abstract

Zhaoming Zhong1,2,*, Zedong Hu1,*, Yue Jiang1, Ruimei Sun1, Xue Chen1, Hongying Chu1, Musheng Zeng3, Chuanzheng Sun1

1Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China

2Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China

3State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Musheng Zeng, email: mushengzeng@163.com

Chuanzheng Sun, email: scz008@126.com

Keywords: anaplastic thyroid carcinoma, interleukin-11, epithelial-mesenchymal transition, metastasis, hypoxia-inducible factor-1α

Received: September 13, 2015    Accepted: June 29, 2016    Published: July 25, 2016

ABSTRACT

Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored.


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