| RRC ID |
55959
|
| 著者 |
Ichimanda M, Hijiya N, Tsukamoto Y, Uchida T, Nakada C, Akagi T, Etoh T, Iha H, Inomata M, Takekawa M, Moriyama M.
|
| タイトル |
Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of ERKs in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with an MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. In contrast, ERKs in the deep region were markedly hyperactivated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.
|
| 巻・号 |
109(1)
|
| ページ |
250-258
|
| 公開日 |
2018-1-1
|
| DOI |
10.1111/cas.13444
|
| PMID |
29150975
|
| PMC |
PMC5765293
|
| MeSH |
Aged
Cell Line, Tumor
Cell Proliferation
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism*
Down-Regulation*
Dual-Specificity Phosphatases / genetics*
Dual-Specificity Phosphatases / metabolism*
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Male
Middle Aged
Mitogen-Activated Protein Kinase Phosphatases / genetics*
Mitogen-Activated Protein Kinase Phosphatases / metabolism*
Neoplasm Invasiveness
Phosphorylation
|
| IF |
4.751
|
| 引用数 |
7
|
| リソース情報 |
| ヒト・動物細胞 |
COLO-320(RCB1193)
CW-2(RCB0778) |
