The biological roles of YAP in malignant mesothelioma proliferation and invasion

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590375
• Research Category: Grant-in-Aid for Scientific Research (C)
• 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: MURAKAMI Hideki 愛知医科大学, 医学部, 准教授 (90303619)
• Project Period (FY): 2010 – 2012
• 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.

Research Products

• [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.
  • Journal Title: Oncogene Volume: 31 Pages: 5117-22
  • DOI: doi:10.1038/onc.2012.5.
  • Peer Reviewed
• [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.
  • Journal Title: J Thorac Oncol. Volume: 7 Pages: 890-899
  • DOI: doi:10.1097/JTO.0b013e31824af2db
  • Peer Reviewed
• [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.
  • Journal Title: J Exp Med. Volume: 209(3) Pages: 479-494
  • DOI: doi:10.1084/jem.20111653
  • Peer Reviewed
• [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.
  • Journal Title: Cancer Res. Volume: 71(3) Pages: 873-883
  • DOI: doi:10.1158/0008-5472.CAN-09-1595
  • Peer Reviewed
• [Journal Article] Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by a new compound JBIR-23. (2011)
  • Author(s): Hwang, J. H., Takagi, M., Murakami, H., Sekido, Y., Shin-ya, K.
  • Journal Title: Cancer Lett. Volume: 300(2) Pages: 189-196
  • DOI: doi:10.1016/j.canlet.2010.10.005
  • Peer Reviewed
• [Presentation] 悪性中皮腫におけるBAP1遺伝子異常の検討 (2012)
  • Author(s): 石黒太志、村上秀樹、水野鉄也、谷口哲郎、横井香平、関戸好孝
  • Organizer: 第53回癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-09
• [Presentation] 高密度CGHアレイを用いた悪性中皮腫細胞株における染色体欠失・増幅領域の網羅的解析 (2010)
  • Author(s): 村上秀樹、谷口哲郎、水野鉄也、石黒太志、関戸好孝
  • Organizer: 第51回肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-04
• [Presentation] Expression and functional analysis of Hairy Enhancer of Split 1(HES1) in human malignantmesothelioma cell lines. (2010)
  • Author(s): Murakami H, Kawada S, Taniguchi T, Kawaguchi K, Mizuno T, Ishiguro F, Fujii M, Kondo Y, Osada H, Sekido Y
  • Organizer: The 10th International Conference of the International Mesothelioma Intrest Group
  • Place of Presentation: 京都
  • Year and Date: 2010-09-02
• [Remarks]
  • URL: http://www.aichi-med-u.ac.jp/