Model mouse for malignant colorectal cancer progression

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Nakayama Mizuho 金沢大学, がん進展制御研究所, 助教 (20398225)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 大腸がん / マウスモデル / 転移 / 再発

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.

Free Research Field

腫瘍生物学