| RRC ID |
36028
|
| 著者 |
Ida L, Yamaguchi T, Yanagisawa K, Kajino T, Shimada Y, Suzuki M, Takahashi T.
|
| タイトル |
Receptor tyrosine kinase-like orphan receptor 1, a target of NKX2-1/TTF-1 lineage-survival oncogene, inhibits apoptosis signal-regulating kinase 1-mediated pro-apoptotic signaling in lung adenocarcinoma.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
We previously identified receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a transcriptional target of the NKX2-1/TTF-1 lineage-survival oncogene in lung adenocarcinoma. ROR1 consequently sustains a favorable balance between pro-survival phosphatidylinositol 3-kinase-protein kinase B and pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1)-p38MAPK signaling. In contrast to recent advances in understanding how ROR1 sustains pro-survival signaling, the mechanism of ROR1 repression of pro-apoptotic signaling remains rather elusive. In the present study, we investigated the underlying mechanism of ROR1-mediated inhibition of the ASK1-p38MAPK signaling pathway. Growth inhibition mediated by siROR1 was partially but significantly alleviated by ASK1 co-knockdown in lung adenocarcinoma cell lines. Also, ASK1 phosphorylation at Thr845, which reflects its activated state, was clearly inhibited by ROR1 overexpression in both steady state and oxidative stress-elicited conditions in MSTO-211H cells. In addition, we found that ROR1 was physically associated with ASK1 at the C-terminal serine threonine-rich domain of ROR1. Furthermore, ROR1 kinase activity was shown to be required to repress the ASK1-p38 axis and oxidative stress-induced cell death. The present findings thus support our notion that ROR1 sustains lung adenocarcinoma survival, at least in part, through direct physical interaction with ASK1 and consequential repression of the pro-apoptotic ASK1-p38 axis in a ROR1 kinase activity-dependent manner.
|
| 巻・号 |
107(2)
|
| ページ |
155-61
|
| 公開日 |
2016-2-1
|
| DOI |
10.1111/cas.12858
|
| PMID |
26661061
|
| PMC |
PMC4768386
|
| MeSH |
Adenocarcinoma / metabolism*
Apoptosis / physiology
Blotting, Western
Cell Line, Tumor
DNA-Binding Proteins / metabolism
Flow Cytometry
Gene Expression Regulation, Neoplastic / physiology*
Humans
Immunoprecipitation
Lung Neoplasms / metabolism*
MAP Kinase Kinase Kinase 5 / metabolism*
Nuclear Proteins / metabolism
Oncogenes
RNA, Small Interfering
Receptor Tyrosine Kinase-like Orphan Receptors / metabolism*
Signal Transduction / physiology
Thyroid Nuclear Factor 1
Transcription Factors / metabolism
Transfection
|
| IF |
4.966
|
| 引用数 |
6
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| 遺伝子材料 |
Genome Network Project Human cDNA IRAK110J03 (HGX044219) |
| ヒト・動物細胞 |
PC-9(RCB4455) |
