| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| Research Abstract |
A recent comprehensive analysis of human cancer has demonstrated that GCF2/LRRFIP1 is one of the cancer associated genes that are categorized as transcriptional regulators. Up to now, however, the precise relationship between the GCF2 expression and carcinogenesis has not been established. Recently, a new function of GCF2 as a regulator of cell migration through the RhoA activity was identified. From these works, I hypothesized that GCF2 may regulate cancer cell invasion or metastasis. To clarify the metastatic potential of GCF2 in colorectal cancer, I established HT-29 cells stably suppressing the GCF2 expression and injected them into the spleen of the SCID mouse. In this work, we found GCF2 suppression reduced the number of liver metastases. Furthermore, mechanistic analyses indicated that the inhibition of GCF2 reduced the fibronectin induced cell adhesion, migration and invasion activities. Downstream the integrin signaling pathways, GCF2 regulate the activity of RhoA interacting with the RGS domain of Leukemia associated RhoGEF (LARG). These results suggest that GCF2 has an important role in colorectal cancer cells metastasis regulating the RhoA induced cell adhesion, migration and invasion activity.
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