| セッション情報 |
The 2nd JSGE International Topic Conference Poster Session
Caricinogenesis of Colon Cancer
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| タイトル |
IT-P-15：Wnt/β-Catenin Signaling during Intestinal Tumorigenesis Requires Cdc42 Activity
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| 演者 |
Sakamori Ryotaro（Department of Gastroenterology and Hepatology, Osaka University School of Medicine, Japan） |
| 共同演者 |
Gao Nan（Department of Biological Sciences, Rutgers University, USA）, Takehara Tetsuo（Department of Gastroenterology and Hepatology, Osaka University, Japan） |
| 抄録 |
Genetic tracing experiments in mice have revealed that intestinal stem cells harboring gain-of-function mutations in Wnt/β-Catenin signaling components expand rapidly into the resultant colorectal cancer tissues. However, critical intracellular machineries that mediate and/or amplify the pathway activities during the tumorigenesis have not been fully defined. This has prevented strategic intervention of Wnt-dependent tumor development. We demonstrate that the mouse colonic or intestinal cancers express elevated levels of Cdc42, a small GTPase of the Rho subfamily. We find that intestine-specific ablation of Cdc42 leads to reduced stem cell clonal expansion and increased crypt cell death. In multiple Wnt-activating mutant genetic backgrounds, deletion of one allele of Cdc42 significantly attenuates tumor growth and prolongs the survival time of the cancer-bearing animals. Canonical Wnt activates Cdc42 activity which may contributes to the abnormal cytoskelton reorganization during tumorigenesis. And inhibition of Cdc42 attenuates Wnt signaling activity. Using gene ablation, we show that Cdc42 is critical in both Wnt-secreting and -responsive cells for the maintenance of the Wnt signal production and transduction. Our data suggest that Cdc42 is a potential target for the molecular intervention of colorectal cancers. |
| 索引用語 |
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