2023 Fiscal Year Annual Research Report
The role of activin combined with different gene mutations in colorectal cancer EMT
| Project/Area Number |
21K15502
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
WANG DONG 金沢大学, ナノ生命科学研究所, 特任助教 (20842983)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | activin / driver gene mutation / colorectal cancer / EMT |
|---|
| Outline of Annual Research Achievements |
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.
|
