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

被引：35

作者：

Bak, Yesol ^{[1
,2
]}

Kwon, Taeho ^{[1
,2
]}

Bak, In Seon ^{[2
]}

Hong, Jintae ^{[3
]}

Yu, Dae-Yeul ^{[2
]}

Yoon, Do-Young ^{[1
]}

机构：

[1] Konkuk Univ, Dept Biosci & Biotechnol, Bio Mol Informat Ctr, Seoul, South Korea

[2] KRIBB, Dev & Differentiat Res Ctr, Dis Model Res Lab, Aging Intervent Res Ctr, Daejeon, South Korea

[3] Chungbuk Natl Univ, Coll Pharm, Cheongju, Chungbuk, South Korea

来源：

ONCOTARGET | 2016年 / 7卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

IL-32; cancer stem cells; stemness; EMT; colon cancer; NF-KAPPA-B; SIGNALING PATHWAY; COLORECTAL-CANCER; INITIATING CELLS; ACTIVATION; INVASION; GROWTH; IDENTIFICATION; INACTIVATION; EXPRESSION;

D O I：

10.18632/oncotarget.7007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：7307 / 7317

页数：11

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