| RRC ID |
62880
|
| 著者 |
Ratsada P, Hijiya N, Hidano S, Tsukamoto Y, Nakada C, Uchida T, Kobayashi T, Moriyama M.
|
| タイトル |
DUSP4 is involved in the enhanced proliferation and survival of DUSP4-overexpressing cancer cells.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Dual-specificity phosphatase 4 (DUSP4), a MAP kinase phosphatase, has been regarded as a tumor suppressor gene in several cancers. However, high-level expression of DUSP4 is occasionally observed in specific cancers and its functional significance in carcinogenesis is not fully understood. In the present study, we showed that downregulation of DUSP4 suppressed the proliferation of cancer cell lines exhibiting high expression of DUSP4 by inducing apoptosis and cell cycle arrest at G2/M phase. Expression microarray analyses and pathway analyses revealed that downregulation of DUSP4 activated the p53 signaling pathway, and might be involved in cell growth suppression. Aberrant accumulation of p53 and induction of p53 downstream target genes were further investigated. Furthermore, cell growth suppression following downregulation of DUSP4 was markedly attenuated in p53-deleted cells established using the CRISPR/Cas9 system. These findings suggest that constitutive expression of DUSP4 in cancer cells contributes to enhanced proliferation through escape from apoptosis and cell cycle arrest. We propose that DUSP4 could be a novel therapeutic target for cancers overexpressing it.
|
| 巻・号 |
528(3)
|
| ページ |
586-593
|
| 公開日 |
2020-7-30
|
| DOI |
10.1016/j.bbrc.2020.05.140
|
| PII |
S0006-291X(20)31068-8
|
| PMID |
32505357
|
| MeSH |
Apoptosis / genetics
Apoptosis / physiology
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Cell Line, Tumor
Cell Proliferation / genetics
Cell Proliferation / physiology
Cell Survival / genetics
Cell Survival / physiology
Down-Regulation
Dual-Specificity Phosphatases / genetics
Dual-Specificity Phosphatases / metabolism*
G2 Phase Cell Cycle Checkpoints / genetics
G2 Phase Cell Cycle Checkpoints / physiology
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
HCT116 Cells
Humans
Mitogen-Activated Protein Kinase Phosphatases / genetics
Mitogen-Activated Protein Kinase Phosphatases / metabolism*
Neoplasms / enzymology*
Neoplasms / genetics
Neoplasms / pathology*
Signal Transduction / genetics
Signal Transduction / physiology
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
HCT116(RCB2979) |
