| 研究実績の概要 |
In this project, we found that Kras and p53 mutation regulate the functional switch of TGFβ signaling pathway. To reveal the detailed mechanism, we performed RNA-seq and found that expression of Hmga2 was significantly upregulated in organoids with Trp53 GOF/LOH alterations. Importantly, loss of HMGA2 suppressed expression of Twist1 and blocked activin A-induced partial EMT and metastasis in Trp53 GOF/LOH organoids. In addition, we found that human tumors carried Trp53 GOF/LOH mutations formed more metastasis than the tumor carried wild type p53. What’s more, knockout of mutated p53 in human colon cancer cell lines suppressed TGFβ-induced invasion, indicating that p53 mutation is important for EMT process.
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