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DUSP4 is involved in the enhanced proliferation and survival of DUSP4-overexpressing cancer cells.
Metadata
Journalbiochemical and biophysical research communications2.985Date
2020 Jun 03
4 months ago
Type
Journal Article
Volume
2020-Jul-30 / 528 : 586-593
Author
Ratsada P 1, Hijiya N 2, Hidano S 3, Tsukamoto Y 1, Nakada C 4, Uchida T 1, Kobayashi T 3, Moriyama M 1
Affiliation
  • 2. Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan. Electronic address: [email protected]
  • 3. Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita, Japan.
  • 4. Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan; Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
Doi
PMIDMESH
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.
Keywords: Apoptosis Cell cycle arrest DUSP4 Proliferation p53 signaling pathway
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Biochem Biophys Res Communbiochemical and biophysical research communications
Metadata
LocationUnited States
FromACADEMIC PRESS INC ELSEVIER SCIENCE

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