IL-32θ inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer

Oncotarget
Yesol BakDo-Young Yoon

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 u...Continue Reading

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Citations

Jul 31, 2012·Gastroenterology·Guoqiang HuaRichard Kolesnick
Mar 22, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Mircea BeuranSorin Hostiuc
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Jun 3, 2021·International Journal of Molecular Sciences·Thu-Huyen PhamDo-Young Yoon

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Methods Mentioned

BETA
flow cytometry
pulldown
nuclear translocation
Pull-down
xenograft
xenografts
surgical resection
electrophoresis
confocal microcopy
column chromatography

Software Mentioned

CellQuest

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