| RRC ID |
64630
|
| 著者 |
Imura Y, Nakai T, Yamada S, Outani H, Takenaka S, Hamada K, Araki N, Itoh K, Yoshikawa H, Naka N.
|
| タイトル |
Functional and therapeutic relevance of hepatocyte growth factor/c-MET signaling in synovial sarcoma.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with a poor prognosis and, thus, novel therapeutic strategies for SS are urgently required. In the present study, we investigated the functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells. c-MET-activated Yamato-SS cells showed higher anchorage-independent growth ability and less sensitivity to chemotherapeutic agents than did c-MET-inactivated SYO-1 or HS-SY-II cells. INC280, a selective c-MET inhibitor, inhibited growth of Yamato-SS cells both in vitro and in vivo but not that of SYO-1 or HS-SY-II cells. INC280 induced cell cycle arrest and apoptosis, and blocked phosphorylation of c-MET and its downstream effectors in Yamato-SS cells. Co-expression of HGF and c-MET in SS clinical samples correlated with a poor prognosis in patients with SS. Taken together, activation of HGF/c-MET signaling in an autocrine fashion leads to an aggressive phenotype in SS and targeting of this signaling exerts superior antitumor effects on c-MET-activated SS. HGF/c-MET expression status is a potential biomarker for identification of SS patients with a worse prognosis who can benefit from c-MET inhibitors.
|
| 巻・号 |
107(12)
|
| ページ |
1867-1876
|
| 公開日 |
2016-12-1
|
| DOI |
10.1111/cas.13092
|
| PMID |
27779808
|
| PMC |
PMC5198956
|
| MeSH |
Animals
Antineoplastic Agents / pharmacology
Autocrine Communication
Cell Line, Tumor
Cell Proliferation / drug effects
Disease Models, Animal
Gene Expression
Gene Silencing
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / metabolism*
Hepatocyte Growth Factor / pharmacology
Heterografts
Humans
Mice
Prognosis
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins c-met / metabolism*
Sarcoma, Synovial / genetics
Sarcoma, Synovial / metabolism*
Sarcoma, Synovial / mortality
Signal Transduction* / drug effects
|
| IF |
4.966
|
| リソース情報 |
| ヒト・動物細胞 |
HS-SY-II(RCB2231) |
