Oncotarget

Research Papers:

Synergistic inhibition effect of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib on IL-6-induced proliferation and Wnt signaling pathway in human multiple myeloma cells

Yura Lee, Jung-Il Jung, Kyeong-Yong Park, Soon Ae Kim and Jiyeon Kim _

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Oncotarget. 2017; 8:41091-41101. https://doi.org/10.18632/oncotarget.17056

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Abstract

Yura Lee1,4, Jung-Il Jung1, Kyeong-Yong Park2, Soon Ae Kim3 and Jiyeon Kim1

1Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Korea

2R&D Center, Peptron, Inc., Daejeon 34054, Korea

3Department of Pharmacology, School of Medicine, Eulji University, Daejeon 34824, Korea

4Present address: Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul 03722, Korea

Correspondence to:

Jiyeon Kim, email: yeon@eulji.ac.kr

Keywords: multiple myeloma, TNIK, KY-05009, IL-6, Wnt signaling

Received: December 06, 2016     Accepted: March 21, 2017     Published: April 12, 2017

ABSTRACT

Multiple myeloma is a fetal form of plasma cell malignancy characterized by abnormal clonal proliferation of plasma cells. Especially, the canonical Wnt signaling pathway mediated by β-catenin is activated in multiple myeloma cells, stimulating their proliferation. Here, we investigated the relationship between interleukin-6-induced proliferation of multiple myeloma cells and Traf2- and Nck-interacting kinase (TNIK) expression in Wnt signaling. Interleukin-6 increased the proliferation of multiple myeloma cells and TNIK mRNA and protein expression. In addition, we examined the effect on TNIK of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib and whether inhibition of TNIK suppresses the interleukin-6-induced proliferation of multiple myeloma cells. KY-05009 and dovitinib synergistically inhibited interleukin-6-stimulated proliferation and induced apoptosis through the inhibition of Wnt signaling in MM cells. Our results provide crucial information that TNIK is involved in the interleukin-6-dependent proliferation of multiple myeloma cells and inhibition of Wnt signaling involving TNIK could be a therapeutic strategy for the treatment of interleukin-6-dependent multiple myeloma.


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