Journal
ONCOTARGET
Volume 7, Issue 6, Pages 7307-7317Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7007
Keywords
IL-32; cancer stem cells; stemness; EMT; colon cancer
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Funding
- National Research Foundation of Korea (NRF) [2015R1A2A2A09001137]
- KRIBB Research Initiative Program of Korea [KGM3141521]
- NRF [2012-0006686]
- National Research Council of Science & Technology (NST), Republic of Korea [KGM3141521] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2015R1A2A2A09001137] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Interleukin (IL)-32 is a well-known cytokine associated with inflammation, virus infections and cancer. IL-32 theta is a newly identified isoform of IL-32, whose function has yet to be elucidated. In this study, we investigated IL-32 theta function in colon cancer stem cells. Using samples from colon cancer patients, we found that the expression of IL-32 theta mRNAs was significantly suppressed in tumor regions. We investigated the effects of IL-32 theta on colon cancer. Ectopic expression of IL-32 theta attenuated invasion, migration in vitro and in vivo tumorigenicity of colon cancer cells. IL-32 theta inhibited epithelial-mesenchymal transition (EMT), resulting in the suppression of their migratory and invasive capabilities of HT29 colon cancer cells. In addition, IL-32 theta altered various properties of CSCs, including sphere formation and expression of stemness related genes. IL-32 theta directly bound to STAT3 and inhibited its nuclear translocation, leading to inhibited transcription of downstream factors, including Bmi1 and ZEB1. We showed that IL-32 theta inhibited the STAT3-ZEB1 pathway and consequently inhibited key factors of stemness and EMT. Taken together, our findings reveal that IL-32 theta can be a tumor suppressor, indicating that IL-32 theta could possibly be used in therapies for colon cancer.
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