2012 Fiscal Year Final Research Report
Regulatory mechanism of the tumor suppressive Hippo pathway
| Project/Area Number |
22590267
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HATA Yutaka 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (80313237)
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| Co-Investigator(Renkei-kenkyūsha) |
NAKAGAWA Kentaro 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (70451929)
IKEDA Mitsunobu 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (00451930)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 癌 / シグナル伝達 / キナーゼ / tumor suppressor |
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| Research Abstract |
To clarify the molecular mechanism that regulates the mammalian Hippo pathway, we first searched for molecules that functionally and physically interact with the known components such as FAT4, Merlin, RASSFs, Salvador, and MOB1. However, this attempt was not successful. We subsequently established several cell-based assay systems to monitor the activity of the Hippo pathway and searched for chemical compounds that up-regulate or down-regulate the Hippo pathway. We found that ss-adrenergic stimulants up-regulate the Hippo pathway. This is the first study to report the implication of G protein-coupled receptors in the regulation of the Hippo pathway. We have additionally obtained several candidate compounds that modulate the Hippo pathway. These compounds include candidates that promote myogenesis and that inhibit cancer invasiveness and metastasis. We are currently analyzing how these compounds exhibit the effects and trying to find out new regulatory mechanisms of the Hippo pathway as well as to develop useful reagents for the treatment of muscle atrophy and cancer. We also analyzed Caenorhabditis elegans homologs of RASSF and YAP, both of which are the components of the Hippo pathway, and found that the Hippo pathway is not conserved in Caenorhabditis elegans. However the findings about Caenorhabditis elegans RASSF homolog has shed light on the putative function of RASSF, which may be useful for the future study in the mammalian Hippo pathway.
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[Journal Article] Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans2013
Author(s)
Iwasa H, Maimaiti S, Kuroyanagi H, Kawano S, Inami K, Timalsina S, Ikeda M, Nakagawa K, Hata Y
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Journal Title
Exp.Cell Res
Volume: 319
Pages: 931-945
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[Journal Article] Cancer susceptibility and embryonic lethality in Mob1A/1B double mutant mice2012
Author(s)
Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F, Chiba S, Mizuno K, Suzuki S, Dong Y, Tokuda M, Morikawa T, Hikasa H, Eggenschwiler J, Yabuta N, Nojima H, Nakagawa K, Hata Y, Nishina H, Mimori K, Mori M, Sasaki T, Mak TW, Nakano T,Itami S, Suzuki A
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Journal Title
J. Clin. Invest
Volume: 122
Pages: 4505-4518
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[Journal Article] SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapse2011
Author(s)
Fukaya M, Kamata A, Hara Y, Tamaki H, Katsumata O, Ito N, Takeda S, Hata Y, Suzuki T, Watanabe M, Harvey RJ,Sakagami H
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Journal Title
J. Neurochem
Volume: 116
Pages: 1122-1137
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[Journal Article] Filamin associates with stress signaling kinases MKK7 and MKK4 and regulates JNKactivation2010
Author(s)
Nakagawa K, Sugahara M, Yamasaki T, Kajiho H, Takahashi S, Hirayama J, Minami Y, Ohta Y, Watanabe T, Hata Y, Katada T, Nishina H
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Journal Title
Biochem. J
Volume: 427
Pages: 237-245
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