Journal
CANCER LETTERS
Volume 375, Issue 2, Pages 390-399Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.03.012
Keywords
Cancer stem cell; Non-cancer stem cell; IL-17E; IL-17RB; Human hepatocellular carcinoma
Categories
Funding
- National Natural Sciences Foundation of China [81520108025, 81330048, 81472292, 81301959]
- National Basic Research Program of China (973 Program) [2010CB529406]
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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-kappa B 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-kappa B signaling. All the findings indicated that non-CSC-derived secreted IL-17E binds IL-17RB on CSCs to signal via JAK/Stat3 and NF-kappa B pathways to mediate crosstalk between CSCs and non-CSCs. Therefore, IL-17E/IL-17RB signaling represents a potential therapeutic target for treatment of HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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