RRC ID 63501
著者 Kato T, Inoue H, Imoto S, Tamada Y, Miyamoto T, Matsuo Y, Nakamura Y, Park JH.
タイトル Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells.
ジャーナル Oncotarget
Abstract T-lymphokine-activated killer cell-originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.
巻・号 7(14)
ページ 17652-64
公開日 2016-4-5
DOI 10.18632/oncotarget.7755
PII 7755
PMID 26933922
PMC PMC4951240
MeSH Apoptosis / drug effects Carcinoma, Renal Cell / drug therapy* Carcinoma, Renal Cell / enzymology Carcinoma, Renal Cell / genetics Carcinoma, Renal Cell / pathology Cell Line, Tumor Cell Proliferation / drug effects Down-Regulation Forkhead Box Protein M1 / biosynthesis Forkhead Box Protein M1 / genetics Forkhead Box Protein M1 / metabolism Gene Knockdown Techniques Humans Kidney Neoplasms / drug therapy* Kidney Neoplasms / enzymology Kidney Neoplasms / pathology Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors* Mitogen-Activated Protein Kinase Kinases / biosynthesis Mitogen-Activated Protein Kinase Kinases / genetics Mitogen-Activated Protein Kinase Kinases / metabolism Molecular Targeted Therapy Phosphorylation Protein Kinase Inhibitors / pharmacology* Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / biosynthesis Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Small Molecule Libraries / pharmacology Transfection
IF 5.168
リソース情報
ヒト・動物細胞 OS-RC-2(RCB0735) TUHR10TKB(RCB1275) TUHR14TKB(RCB1383)