Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation.
Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation.
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Interleukin-11 通过 PI3K/Akt/GSK3β 信号通路激活促进未分化甲状腺癌细胞的上皮间质转化
DOI：
10.18632/oncotarget.10831
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Zhong Z;Hu Z;Jiang Y;Sun R;Chen X;Chu H;Zeng M;Sun C
转移是甲状腺未分化癌（ATC）患者治疗失败的主要原因。在初步研究中，我们证明白细胞介素（IL）-11的表达与ATC的远处转移呈正相关。然而，其背后的机制仍然很大程度上未知。在这里，我们发现氯化钴（一种缺氧模拟物）通过 HIF-1α 激活促进 IL-11 表达。此外，IL-11表达的增加显着诱导ATC细胞的上皮-间质转化（EMT），伴随着Akt/GSK3β通路的激活以及侵袭和迁移能力的增加。相反，HIF-1α 或 IL-11 敲低，或用针对 IL-11 的中和抗体、PI3K 抑制剂或 Akt 抑制剂 V 处理细胞，可显着抑制 EMT 的诱导，并抵消侵袭和迁移能力的增强。这些结果表明，缺氧通过 HIF-1α 诱导增加 ATC 细胞中 IL-11 的分泌，然后 IL-11 通过 PI3K/Akt/GSK3β 途径诱导这些细胞中的 EMT，最终提高其侵袭和迁移潜力。这项研究阐明了 IL-11 在 ATC 转移中发挥的促转移作用，并表明它是治疗癌症转移的潜在靶点。然而，许多问题仍有待探讨。
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.