Open AccessNovel Interleukin-6 Inducible Gene PDZ-Binding Kinase Promotes Tumor Growth of Multiple Myeloma Cells
Author(s) -
Akinobu Ota,
Ichiro Hanamura,
Sivasundaram Karnan,
Shingo Inaguma,
Norio Takei,
Vu Quang Lam,
Shohei Mizuno,
Jo Kanasugi,
Md Wahiduzzaman,
Lutfur Rahman,
Toshinori Hyodo,
Hiroyuki Konishi,
Shinobu Tsuzuki,
Hiroshi Ikeda,
Akiyoshi Takami,
Yoshitaka Hosokawa
Publication year - 2020
Publication title -
journal of interferon and cytokine research
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 94
eISSN - 1557-7465
pISSN - 1079-9907
DOI - 10.1089/jir.2020.0111
Subject(s) - cancer research , in vivo , pdz domain , biology , multiple myeloma , kinase , apoptosis , malignancy , gene knockdown , microbiology and biotechnology , immunology , genetics
[Figure: see text] Multiple myeloma (MM) remains an intractable hematological malignancy, despite recent advances in anti-MM drugs. Here, we show that role of PDZ binding kinase (PBK) in MM tumor growth. We identified that interleukin-6 (IL-6) readily increases PBK expression. Kaplan-Meier analysis showed that the MM patients with higher expression of PBK have a significant shorter survival time compared with those with moderate/lower expression of PBK. Knockout of PBK dramatically suppressed in vivo tumor growth in MM cells, while genome editing of PBK changing from asparagine to serine substitution (rs3779620) slightly suppresses the tumor formation. Mechanistically, loss of PBK increased the number of apoptotic cells with concomitant decrease in the phosphorylation level of Stat3 as well as caspase activities. A novel PBK inhibitor OTS514 significantly decreased KMS-11-derived tumor growth. These findings highlight the novel oncogenic role of PBK in tumor growth of myeloma, and it might be a novel therapeutic target for the treatment of patients with MM.