Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells
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Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induced caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs. Our results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway.
KeywordsTNIK Dovitinib Wnt signaling Multiple myeloma IM-9 Apoptosis
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and by a grant from the Ministry of Science, ICT and Future Planning (NRF-2014R1A1A1002349).
Compliance with ethical standards
All procedures that were performed in the studies involving human participants were in accordance with the ethical standards of the International Review Board of Eulji University (EU 15-06), with the 1964 Helsinki declaration and its later amendments.
Conflict of interest
All authors declare that they have no conflict of interest.
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