2012 Fiscal Year Final Research Report
The biological roles of YAP in malignant mesothelioma proliferation and invasion
Project/Area Number |
22590375
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Aichi Medical University (2011-2012) Aichi Cancer Center Research Institute (2010) |
Principal Investigator |
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Project Period (FY) |
2010 – 2012
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Keywords | 腫瘍 |
Research Abstract |
We recently revealed malignant mesothelioma cell lines frequently harbor mutations of the genes associated with Hippo tumor suppressor pathway. Dysregulation of Hippo pathway leads to activation of a transcriptional co-activator Yes-associated protein (YAP) and the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ). However the detailed function of YAP/TAZ on MM cell growth or motility remains unclear. To investigate the biological roles of YAP/TAZ in MM development, we generated lentivirus mediated YAP or TAZ knock-down system in MM cells, and analyzed the changes in cell growth, motility, and the gene expression patterns with oligonucleotide microarrays. SiRNA mediated reduction of YAP/TAZ in MM cell lines suppress cell proliferation and motility. We also detected the deregulation of several genes involved in cell proliferation, apoptosis, and cytoskeleton by YAP/TAZ knockdown. Our results will provide new insights into development of mesothelioma, and give some clues to developing a new molecular target therapy for mesothelioma.
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[Journal Article] YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes.2012
Author(s)
Mizuno, T., Murakami, H., Fujii, M., Ishiguro, F., Tanaka, I., Kondo, Y., Akatsuka, S., Toyokuni, S., Yokoi, K., Osada, H., Sekido, Y.
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Journal Title
Oncogene
Volume: 31
Pages: 5117-22
DOI
Peer Reviewed
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[Journal Article] Activated leukocyte cell-adhesion molecule (ALCAM) promotes malignant phenotypes of malignant mesothelioma.2012
Author(s)
Ishiguro, F., Murakami, H., Mizuno, T., Fujii, M., Kondo, Y., Usami, N., Yokoi, K., Osada, H., Sekido, Y.
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Journal Title
J Thorac Oncol.
Volume: 7
Pages: 890-899
DOI
Peer Reviewed
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[Journal Article] TGF-beta synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.2012
Author(s)
Fujii, M., Toyoda, T., Nakanishi, H., Yatabe, Y., Sato, A., Matsudaira, Y., Ito, H., Murakami, H., Kondo, Y., Kondo, E., Hida, T., Tsujimura, T., Osada, H., Sekido, Y.
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Journal Title
J Exp Med.
Volume: 209(3)
Pages: 479-494
DOI
Peer Reviewed
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[Journal Article] LATS2 is a tumor suppressor gene ofmalignant mesothelioma.2011
Author(s)
Murakami, H., Mizuno, T., Taniguchi, T., Fujii, M., Ishiguro, F., Fukui, T., Akatsuka, S., Horio, Y., Hida, T., Kondo, Y., Toyokuni, S., Osada, H.,Sekido, Y.
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Journal Title
Cancer Res.
Volume: 71(3)
Pages: 873-883
DOI
Peer Reviewed
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