| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We found that forkhead transcription factor FOXF1 and intercellular adhesion molecule-2 (ICAM2) are novel target genes of p53. The ectopic expression of FOXF1 and ICAM2 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 and ICAM2 stimulated cell invasion and migration. Our findings suggest that FOXF1 and ICAM2 induction by p53 are on key pathways in inhibiting cancer cell migration and invasion.
We also found CRKL oncogene is downregulated by p53 through miR-200s. First, we identified that miR-200s are direct transcriptional targets of p53 and then miR-200b/200c/429 inhibited CRKL mRNA and protein expression by directly targeting its 3’-UTR region. The CRKL oncogene encodes an adaptor protein containing Src homology 2 and 3 (SH2/SH3) domains and is reported to be overexpressed in a subset of cancer types. Our results demonstrate that the p53 target miR-200b/200c/429 miRNAs are negative regulators of the CRKL oncogene.
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