title: Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation.
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.
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.|Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Zedong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Ruimei
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Chuanzheng
authors.initials: C
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508611:IL11 protein, human; D017370:Interleukin-11; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: anaplastic thyroid carcinoma; epithelial-mesenchymal transition; hypoxia-inducible factor-1α; interleukin-11; metastasis