@article{oai:repo.qst.go.jp:00047402,
 author = {Fujita, Mayumi and Imadome, Kaori and Shoji, Yoshimi and Isozaki, Teturou and Endo, Satoshi and Yamada, Shigeru and Imai, Takashi and 藤田 真由美 and 今留 香織 and 荘司 好美 and 磯崎 哲朗 and 遠藤 悟史 and 山田 滋 and 今井 高志},
 issue = {1},
 journal = {International Journal of Radiation Oncology Biology Physics},
 month = {May},
 note = {Purpose
This study investigated the mechanisms underlying the inhibition of cancer cell migration and invasion by carbon (C)-ion irradiation.
\nMethods and Materials
Human pancreatic cancer cells MIAPaCa-2, AsPC-1, and BxPC-3 were treated by X-ray (4 Gy) or C-ion (0.5, 1, 2, or 4 Gy) irradiation, and their migration and invasion were assessed 2 days later. The levels of GTP-bound Rac1 and RhoA were determined by the active GTPase pull-down assay with or without a proteasome inhibitor, and the binding of E3 ubiquitin ligase to GTP-bound Rac1 was examined by immunoprecipitation.
\nResults
C-ion irradiation reduced the levels of GTP-bound Rac1 and RhoA, two major regulators of cell motility, in MIAPaCa-2 cells and GTP-bound Rac1 in AsPC-1 and BxPC-3 cells. Proteasome inhibition reversed the effect, indicating that C-ion irradiation induced Rac1 and RhoA degradation via the ubiquitin (Ub)-proteasome pathway. E3 Ub ligase X-linked inhibitor of apoptosis protein (XIAP) which directly targets Rac1, was selectively induced in C-ion irradiated MIAPaCa-2 cells and co-precipitated with GTP-bound Rac1 in C-ion-irradiated cells, which was associated with Rac1 ubiquitination. Cell migration and invasion reduced by C-ion radiation were restored by siRNA-mediated XIAP knockdown, indicating that XIAP is involved in C-ion-induced inhibition of cell motility.
\nConclusion
In contrast to X-ray irradiation, C-ion treatment inhibited the activity of Rac1 and RhoA in MIAPaCa-2 cells and Rac1 in AsPC-1 and BxPC-3 cells via Ub-mediated proteasomal degradation, thereby blocking the motility of these pancreatic cancer cells.},
 pages = {173--180},
 title = {Carbon-ion irradiation suppresses migration and invasiveness of human pancreatic carcinoma cells MIAPaCa-2 via Rac1 and RhoA degradation},
 volume = {93},
 year = {2015}
}