2020 Fiscal Year Final Research Report
The function of TLE3, whose expression correlated with malignancy, on bone invasion and metastasis in melanoma
| Project/Area Number |
19K19241
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | 悪性黒色腫 / TLE3 |
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| Outline of Final Research Achievements |
Melanoma, one of the most aggressive neoplasms, is characterized by rapid cell proliferation. TLE is an important regulator of cell proliferation via HDAC recruitment. Given that HDAC activity is associated with melanoma progression, we examined the relationship between TLE3 and melanoma. TLE3 expression was increased during the progression of human patient melanoma. Overexpression of Tle3 in B16 murine melanoma cells led to an increase in cell proliferation as well as the number of cyclinD1-positive cells. in vivo injection of mice with B16 cells overexpressing Tle3 resulted in larger tumor formation than in mice injected with control cells. In contrast, siRNA-mediated knockdown of Tle3 in B16 cells decreased proliferation. Treatment of B16 cells with trichostatin A, a class I and II HDAC inhibitor, prevented the effect s of Tle3 on proliferation. In conclusion, these data indicate that Tle3 is required, at least in part, for proliferation in the B16 mouse melanoma model.
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| Free Research Field |
歯科麻酔学
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤の登場により，近年メラノーマの治療成績が著しく向上してきた．しかし，これら薬剤が全く無効である症例も少なくなく，さらに間質性肺炎や大腸炎などの免疫関連有害事象をもたらすこともわかってきた．そのため，メラノーマの病態を正確に理解し，新たな治療法を確立する必要性は依然として残っている．HDAC阻害剤はメラノーマの新しい治療薬として注目されている．本課題ではHDACを誘導し転写コファクターとして作用するTLE3がメラノーマの増殖を制御するメカニズムを明らかにしたものであり，HDAC阻害剤を利用したメラノーマの治療に新たなエビデンスを与えることができる研究であったと考える．
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