Correction: Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor
| Autor: | Takashi Miyamoto, Kyoko Kijima, Suyoun Chung, Yusuke Nakamura, Yosuke Harada, Akiko Taira, Naofumi Takamatsu, Yoshiko Fujisawa, Aiko Kudo, Yo Matsuo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Antineoplastic Agents
Mice SCID Protein Serine-Threonine Kinases Mice Mice Inbred NOD Cell Line Tumor Neoplasms Chlorocebus aethiops Biomarkers Tumor Animals Humans Medicine Naphthyridines Phosphorylation Protein Kinase Inhibitors Cell Proliferation Antitumor activity business.industry GTPase-Activating Proteins Correction Xenograft Model Antitumor Assays Neoplasm Proteins Oncology A549 Cells COS Cells Cancer research business Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.27755 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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