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) |