論文 - 詳細
| RRC ID | 62740 |
|---|---|
| 著者 | Chung S, Kijima K, Kudo A, Fujisawa Y, Harada Y, Taira A, Takamatsu N, Miyamoto T, Matsuo Y, Nakamura Y. |
| タイトル | Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor. |
| ジャーナル | Oncotarget |
| 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. |
| 巻・号 | 7(14) |
| ページ | 18171-82 |
| 公開日 | 2016-4-5 |
| DOI | 10.18632/oncotarget.7685 |
| PII | 7685 |
| PMID | 26918358 |
| PMC | PMC4951280 |
| MeSH | A549 Cells Animals Antineoplastic Agents / pharmacology* Biomarkers, Tumor COS Cells Cell Line, Tumor Cell Proliferation / drug effects Chlorocebus aethiops GTPase-Activating Proteins / metabolism* Humans Mice Mice, Inbred NOD Mice, SCID Naphthyridines / pharmacology* Neoplasm Proteins / metabolism* Neoplasms / drug therapy* Neoplasms / pathology Phosphorylation Protein Kinase Inhibitors / pharmacology* Protein Serine-Threonine Kinases / antagonists & inhibitors* Signal Transduction / drug effects Xenograft Model Antitumor Assays |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |