2002 Fiscal Year Final Research Report Summary
Investigation of the mechanism of metastasis induction by D4GDI isolated as a metastasis-inducing gene from human colon cancer cell line
| Project/Area Number |
13671354
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kanazawa Medical University |
|---|
Principal Investigator |
MAEDA Masayo Kanazawa Medical University, Dept. Pathology, Assistant, 医学部, 助手 (30199632)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OTA Takahide Kanazawa Medical University, Medical Research Institute, Associate professor, 総合医学研究所, 助教授 (10152141)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | metastasis / D4GDI / RhoGDI / ERM proteins / Rac / SW480 colon cancer cell line / 1-1ras1000 / metastasis inducing gene / RhoGDI |
|---|
| Research Abstract |
Rho family GTPases play an important role in a number of processes related to metastasis and RhoGDIs regulate Rho family proteins. We cloned genomic DNA capable of transforming non-metastatic ras-transformed 1-1ras1000 cells into metastatic cells, from colon carcinoma SW480 cells. This DNA contained a truncated human ARHGDIB gene, resulting in a C-terminal truncated form of LyGDI (△C-LyGDI, 166-201 deletion), a member of the RhoGDIs. The stable expression of △C-LyGDI induced pulmonary metastasis in 1-1ras1000 cells, whereas cells expressing full-length LyGDI did not metastasize. △C-LyGDI localized preferentially in the membrane and was detected in a NP-40-insoluble fraction, co-purified with Radixin, Moesin, Rac1, Cdcd42, and RhoA. In △C-LyGDI transfectant an activation state of Rac1 was elevated and △C-LyGDI associated with Rac1-GTP. In accordance with the increase of Rac1-GTP level △C-LyGDI transfectants showed higher invasive ability than mock transfectant. These results suggest that LyGDI functions in the cell membrane to afford spatial regulation of Rho family GTPase signaling through ERM proteins during metastasis.
|
Research Products
(8 results)
