Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899346 | Cancer Letters | 2016 | 10 Pages |
Abstract
Within the cancer stem cell (CSC) niche, non-CSCs play an indispensable role in facilitating a microenvironment capable of maintaining CSC properties. Non-CSCs contribute to not only the structure and topology of the tumor microenvironment but also the maintenance of the dynamic state of CSCs. Interleukin-17E (IL-17E/IL-25) is important in allergic inflammation and protection against parasitic infection. Moreover, it has also been demonstrated that IL-17E takes part in different cancers recently. Here, for the first time we demonstrate that discrepant expression of IL-17E and the IL-17 receptor B (IL-17RB) exists in Nanog positive (NanogPos) CSCs and Nanog negative (NanogNeg) non-CSCs in hepatocellular carcinoma (HCC). Moreover, we further demonstrate that IL-17E binding to IL-17RB activates NF-κB and JAK/Stat3 pathways to promote proliferation and sustain self-renewal of CSCs in HCC. Meanwhile, the beneficial effect of IL-17E on NanogPos CSCs could be blocked by specific inhibitors of JAK and NF-κB signaling. All the findings indicated that non-CSC-derived secreted IL-17E binds IL-17RB on CSCs to signal via JAK/Stat3 and NF-κB pathways to mediate crosstalk between CSCs and non-CSCs. Therefore, IL-17E/IL-17RB signaling represents a potential therapeutic target for treatment of HCC.
Keywords
shRNAIL-17RBSCIDRT-PCRNF-kBCSCsGFPFBSDMEMHCCDulbecco's modified Eagle's mediumshort hairpin RNASTATinterleukinTicsfetal bovine serumtumor-initiating cellscancer stem cellCancer stem cellsSignal transducer and activator of transcriptionReverse-transcriptase polymerase chain reactiongreen fluorescent proteinJAKJanus kinasesHuman hepatocellular carcinomaHepatocellular carcinomasevere combined immunodeficiency
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Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Yongli Luo, Zhi Yang, Li Su, Juanjuan Shan, Huailong Xu, Yanmin Xu, Limei Liu, Wei Zhu, Xuejiao Chen, Chungang Liu, Jun Chen, Chao Yao, Feifei Cheng, Chengcheng Zhang, Qinghua Ma, Junjie Shen, Cheng Qian,