| Project/Area Number |
19K07441
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | University of Tsukuba (2021)
Jichi Medical University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | non-TRU type / lung adenocarcinoma / TFF-1 / TTF-1 / HNF4alpha / CADM1 / KRAS / HNF4α / Non-TRU / HNF4A / YAP1 / LATS2 / hippo pathway / Hippo pathway / 肺腺癌 / 消化管上皮分化 |
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| Outline of Research at the Start |
現在、肺腺癌ではEGFR,ALKなどのドライバー変異に対する分子標的薬剤が一定の効果をあげているが、その多くはTTF-1陽性のterminal respiratory unit(TRU)由来の腺癌(TRU-type)であり、Non-TRU typeのドライバー変異は未だ見出されていない。本研究は、Non-TRU typeの肺腺癌のあらたな治療ターゲットを見出すことを目的としている。
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| Outline of Final Research Achievements |
Molecular targeting of Non-TRU type lung adenocarcinomas is still an open field. We focused on TFF-1, which was characteristically highly expressed in non-TRU type cell lines.
We reported that TFF-1 is highly expressed in non-TRU type adenocarcinomas, especially in gastrointestinal epithelial type adenocarcinomas that express high levels of HNF4α, and is involved in apoptosis inhibition and Anoikis resistance, making it a potential therapeutic target (Matsubara, 2020, Cancer Sci).
We also elucidated the mechanism by which CADM1 acts in a tumour suppressive manner via the Hippo pathway in lung adenocarcinoma (Ito, Matsubara. 2019, Cancer Sci).
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| Academic Significance and Societal Importance of the Research Achievements |
TRU-typeの肺腺癌では、EGFR変異、ALK転座、ROS1転座など、様々な分子標的が明らかとなり、予後の改善に貢献しているが、一方で、Non-TRU typeの肺腺癌においては、分子標的は定まっていない。Non-TRU typeの肺腺癌の中でも、胃型の性質を有するMucinous adenocarcinomaは、経気腔的に肺内転移を形成し、Stage I症例においても、極めて予後不良である。我々は、Mucinous adenocarcinomaなどのnon-TRU typeの悪性形質に関わる分子として、Anoikis抵抗性を促すTFF-1を見出し、新たな分子標的となりうることを示した。
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