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• W2327089920 abstract "// Suyoun Chung 1 , Kyoko Kijima 1 , Aiko Kudo 1 , Yoshiko Fujisawa 1 , Yosuke Harada 1 , Akiko Taira 1 , Naofumi Takamatsu 1 , Takashi Miyamoto 1 , Yo Matsuo 1 and Yusuke Nakamura 2 1 OncoTherapy Science, Inc., Kawasaki, Kanagawa, Japan 2 Department of Medicine and Surgery, The University of Chicago, Chicago, IL, USA Correspondence to: Yusuke Nakamura, email: // Keywords : MELK, xenograft model, kinase inhibitor, molecular pharmacology, biomarker Received : December 22, 2015 Accepted : February 08, 2016 Published : February 24, 2016 Abstract MELK is upregulated in various types of human cancer and is known to be associated with cancer progression, maintenance of stemness, and poor prognosis. OTS167, a MELK kinase inhibitor, shows potent growth-suppressive effect on human tumors in a xenograft model, but the detailed mode of action has not been fully elucidated. In this study, we demonstrate the molecular mechanism of action of MELK inhibitor OTS167 in a preclinical model. OTS167-treated cells caused morphological transformation, induced the differentiation markers, and reduced stem-cell marker expression. Furthermore, we identified DEPDC1, known as an oncogene, as an additional downstream molecule of the MELK signaling pathway. MELK enhanced DEPDC1 phosphorylation and its stability. The expression of MELK and downstream molecules was decreased in OTS167-treated xenograft tumor tissues, which revealed central necrosis and significant growth suppression. Our data should further shed light on the mechanism of action how OTS167 suppresses tumor growth through the inhibition of the MELK signaling pathway and suggest the possibility of biomarkers for the assessment of clinical efficacy." @default.
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• W2327089920 date "2016-02-24" @default.
• W2327089920 modified "2023-10-14" @default.
• W2327089920 title "Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor" @default.
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• W2327089920 doi "https://doi.org/10.18632/oncotarget.7685" @default.
• W2327089920 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4951280" @default.
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