2022 Fiscal Year Final Research Report
Genome-wide screening for EMT-MET plasticity in triple-negative breast cancer
| Project/Area Number |
20K07610
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50010:Tumor biology-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 乳癌 / 上皮間葉転換 / EMT / CRISPR/Cas9 |
|---|
| Outline of Final Research Achievements |
Epithelial-mesenchymal transition (EMT), in which epithelial cells lose their characteristics and undergo mesenchymal cell phenotype, and the reverse reaction, MET, are important in various steps of malignant transformation of cancer: EMT enhances resistance to cell death and motility of cancer cells and promotes their migration to blood vessels, the initial stage of metastasis and recurrence after treatment. On the other hand, cancer cells migrating to distant organs recapitulate epithelial-like phenotype through MET and actively proliferate to form metastatic nests. In this study, we performed a comprehensive gene screening using CRISPR/Cas9 and pooled gRNAs to identify genes that regulate EMT/MET plasticity in breast cancer and found several novel EMT-related genes that have not been previously reported to be involved in EMT/MET.
|
| Free Research Field |
分子腫瘍学
|
| Academic Significance and Societal Importance of the Research Achievements |
乳癌は転移が見られないステージ0やステージIでは予後が非常に良いにもかかわらず、転移が見られるステージII以降の症例では5年生存率が急激に低下してしまう。癌細胞の上皮間葉転換(EMT)は転移に密接にかかわることが示唆されており、本研究で実施した新しいEMT関連遺伝子群の探索は癌悪性化の機構解明に繋がるだけでなくEMTを標的とした新しい乳癌治療法開発にも寄与すると考えられ、社会的意義は大きい。
|
