IL-32θ inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer
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Yesol Bak1,2, Taeho Kwon1,2, In seon Bak2, Jintae Hong3, Dae-Yeul Yu2, Do-Young Yoon1
1Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea
2Disease Model Research Laboratory, Aging Intervention Research Center, Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
3College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Korea
Do-Young Yoon, e-mail: [email protected]
Dae-Yeul Yu, e-mail: [email protected]
Keywords: IL-32, cancer stem cells, stemness, EMT, colon cancer
Received: August 03, 2015 Accepted: January 05, 2016 Published: January 25, 2016
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.
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