IL-32θ inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer.
Oncotarget
; 7(6): 7307-17, 2016 Feb 09.
Article
em En
| MEDLINE
| ID: mdl-26824417
ABSTRACT
Interleukin (IL)-32 is a well-known cytokine associated with inflammation, virus infections and cancer. IL-32θ is a newly identified isoform of IL-32, whose function has yet to be elucidated. In this study, we investigated IL-32θ function in colon cancer stem cells. Using samples from colon cancer patients, we found that the expression of IL-32θ mRNAs was significantly suppressed in tumor regions. We investigated the effects of IL-32θ on colon cancer. Ectopic expression of IL-32θ attenuated invasion, migration in vitro and in vivo tumorigenicity of colon cancer cells. IL-32θ inhibited epithelial-mesenchymal transition (EMT), resulting in the suppression of their migratory and invasive capabilities of HT29 colon cancer cells. In addition, IL-32θ altered various properties of CSCs, including sphere formation and expression of stemness related genes. IL-32θ directly bound to STAT3 and inhibited its nuclear translocation, leading to inhibited transcription of downstream factors, including Bmi1 and ZEB1. We showed that IL-32θ inhibited the STAT3-ZEB1 pathway and consequently inhibited key factors of stemness and EMT. Taken together, our findings reveal that IL-32θ can be a tumor suppressor, indicating that IL-32θ could possibly be used in therapies for colon cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Interleucinas
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Neoplasias do Colo
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Fator de Transcrição STAT3
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Transição Epitelial-Mesenquimal
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Recidiva Local de Neoplasia
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article