2019 Fiscal Year Final Research Report
Involvement of Hippo pathway in epigenetic control in lung cancer
| Project/Area Number |
16K08672
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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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| Research Field |
Human pathology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | Hippo pathway / LATS2 / YAP1 / CADM1 / 神経内分泌分化 |
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| Outline of Final Research Achievements |
We revealed that CADM1 forms complexes with Hippo pathway core molecules like MST1/2 and LATS1/2 at the cell membrane, and co-expressions of CADM1 and LATS2 in membrane correlated with better prognosis in primary lung adenocarcinomas (2019, Cancer Sci). We also revealed that loss of YAP1 was characteristics to neuroendocrine tumors of the lung, and YAP1 was correlated with resistance to chemotherapy, and Knock down of YAP1 induced the expression of RAB3A, a neuroendocrine marker (2016, Cancer Sci).
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| Free Research Field |
肺癌病理
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| Academic Significance and Societal Importance of the Research Achievements |
CADM1は腫瘍抑制因子として良く知られるが、接着分子であるCADM1がなぜ腫瘍抑制的に働くのか、その機序の解明は不十分であった。我々は、CADM1がHippo pathwayを介して、腫瘍抑制に働くことを見出した。さらに、Hippo pathwayのターゲット分子であるYAP1のLossが小細胞癌などの神経内分泌腫瘍において特徴的に認められることを見出したのは、我々の報告が最初である。YAP1は細胞分化にも関与している可能性が示された。
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