Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3ß signaling pathway activation.
Oncotarget
; 7(37): 59652-59663, 2016 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-27487122
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/GSK3ß 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/GSK3ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Interleucina-11
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
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Transição Epitelial-Mesenquimal
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Carcinoma Anaplásico da Tireoide
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Glicogênio Sintase Quinase 3 beta
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China