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      Non-CSCs nourish CSCs through interleukin-17E-mediated activation of NF-κB and JAK/STAT3 signaling in human hepatocellular carcinoma.

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          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 (Nanog(Pos)) CSCs and Nanog negative (Nanog(Neg)) 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 Nanog(Pos) 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.

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          Author and article information

          Journal
          Cancer Lett.
          Cancer letters
          Elsevier BV
          1872-7980
          0304-3835
          Jun 01 2016
          : 375
          : 2
          Affiliations
          [1 ] Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
          [2 ] School of Life Science, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
          [3 ] Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: junjiesh@gmail.com.
          [4 ] Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: cqian8634@gmail.com.
          Article
          S0304-3835(16)30150-1
          10.1016/j.canlet.2016.03.012
          27000993
          e74d5135-fa40-45f2-a3f9-506be25a34b9
          History

          Cancer stem cell,Human hepatocellular carcinoma,IL-17E,IL-17RB,Non-cancer stem cell

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