The mechanism for netrin-1 regulated anti-cell death activity and its role in human diseases
| Project/Area Number |
19390092
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East |
|---|
Principal Investigator |
ARAKAWA Hirofumi National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 生物物理部, 部長 (70313088)
|
|---|
| Project Period (FY) |
2007 – 2008
|
| Project Status |
Completed (Fiscal Year 2008)
|
| Budget Amount *help |
¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
|
|---|
| Keywords | 分子腫瘍学 / ネトリン / ネトリンレセプター / アポトーシス / 細胞死 / p53 / 細胞死抑制 / カスペース / 神経軸索誘導 |
|---|
| Research Abstract |
In the present study, we identified a novel netrin-1 receptor X that mediates netrin-1 regulated anti-cell death activity. The interaction of netrin-1 with receptor X not only blocked p53-dependent apoptosis but also induced chemotaxis of both vascular endothelial cells and cancer cells. The interaction led to activation of AKT and Src. In vivo, netrin-1 was colocalized with receptor X at the basement membrane of colorectal epithelial cells. Netrin-1 expression was frequently lost in human colorectal cancer tissues whereas the expression was elevated in cancer stromal region. In 3D culture experiment, the interaction of netrin-1 with receptor X induced cell polarization and growth suppression of colorectal cancer cells. These results suggest that the signaling pathway via netrin-1 and receptor X plays a critical role in cell polarity to suppress tumor initiation and progression.
|
Report
(3 results)
Research Products
(25 results)
-
-
-
-
-
-
[Journal Article] Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion2007
Author(s)
Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chretien D, de Lonlay P, Paquis-Flucklinger V, Arakawa H, Nakamura Y, Munnich A, Rotig A.
-
Journal Title
Nat Genet 39
Pages: 776-780
Related Report
-
-
-
-
[Journal Article] Identification of NEEP21, encoding neuron-enriched endosomal protein of 21kDa, as a transcriptional target of tumor suppressor p53
Author(s)
Ohnishi S, Futamura M, Kamino H, Nakamura Y, Kitamura N, Miyamoto Y, Miyamoto T, Shinogi D, Goda O, Arakawa H.
-
Journal Title
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
