2023 Fiscal Year Final Research Report
Regulation of biological processes by MAPK signaling-inducible genes
| Project/Area Number |
21H02692
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | MAPK / p38 / JNK |
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| Outline of Final Research Achievements |
MAPK signaling pathways regulate various biological processes (e.g., cell proliferation, death, and immune response), and their dysregulation is involved in the etiology of various human diseases, including cancer and autoimmune disorders. In this study, we aimed to elucidate the regulatory mechanisms of biological phenomena involving MAPK signaling and their dysregulation in human diseases. Initially, using an RNA-seq technique, we identified a number of genes whose expression is regulated downstream of MAPK pathways. Of these, we focused on several genes and obtained novel findings regarding their physiological functions. In particular, we found that certain molecules induced by ERK signaling confer resistance to ERK pathway-targeted therapeutics in cancer cells and proposed a novel strategy for cancer therapy targeting these molecules.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
MAPK（ERK/JNK/p38）シグナルの制御破綻は、癌、自己免疫疾患等の病因・病態に深く関与するが、これらの経路の下流でどの様な遺伝子の発現が変化し、最終的に細胞機能が制御されているのかに関しては、未だ不明な点が数多く残されている。本研究により、MAPK経路依存的に発現変動する未知の遺伝子が多数同定されるとともに、これらの遺伝子を介した生命機能の制御メカニズムが分子レベルで明らかとなった。特にERK経路によって発現誘導される特定の遺伝子が、癌細胞の抗癌剤抵抗性獲得に寄与している事を見出すと共に、この分子を人工的に制御することで分子標的抗癌剤の薬効を増強させることが可能であることを示した。
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