Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Outline of Final Research Achievements |
p53 is highly mutated in colorectal cancer (CRC), however, the mechanisms of gain-of-function of mutant p53 in malignant progression have not yet been fully understood. We show that wild-type p53 inhibits nuclear accumulation of mutant p53(R270H), however, relocalization of p53 to nuclei is associated with submucosal invasion and liver metastasis. Moreover, nuclear accumulation of mutant p53 (R270H) causes drastic morphological changes of organoids to complicated glandular architecture, which reflect poorly differentiated histology of in vivo tumors. Furthermore, mutant p53 (R270H) induces expression of wide range of genes through chromatin modification, which results in activation of Wnt/β-catenin pathways, which may be related to stemness and invasiveness. These results provide a novel mechanism of mutant p53 GOF in malignant progression of CRC.
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