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

// Zhaoming Zhong 1, 2, * , Zedong Hu 1, * , Yue Jiang 1 , Ruimei Sun 1 , Xue Chen 1 , Hongying Chu 1 , Musheng Zeng 3 , Chuanzheng Sun 1 1 Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China 2 Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China 3 State 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.