The biological roles of YAP in malignant mesothelioma proliferation and invasion

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍 / 悪性中皮腫 / がん遺伝子 / 細胞内シグナル / 腫瘍抑制遺伝子

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] Membranous expression of activated leukocyte cell adhesion molecule contributes to poor prognosis and malignant phenotypes of non-small-cell lung cancer. (2013)
  • Author(s): Futoshi Ishiguro
  • Journal Title: J Surg Res. Volume: 179 Issue: 1 Pages: 24-32
  • DOI: 10.1016/j.jss.2012.08.044
  • Peer Reviewed
• [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 Issue: 49 Pages: 5117-22
  • 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 F, Kondo Y, Usami N, Yokoi K, Osada H, Sekido Y
  • Journal Title: J Thorac Oncol Volume: 7 Issue: 5 Pages: 890-9
  • DOI: 10.1097/jto.0b013e31824af2db
  • Peer Reviewed
• [Journal Article] TGF-β 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: VOL.209(3) Issue: 3 Pages: 479-494
  • 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) Issue: 23 Pages: 873-883
  • 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) Issue: 2 Pages: 189-196
  • DOI: 10.1016/j.canlet.2010.10.005
  • Peer Reviewed
• [Journal Article] LATS2 is a tumor suppressor gene of malignant mesothelioma (2011)
  • Author(s): Hideki Murakami
  • Journal Title: Cancer Research Volume: 71 Pages: 873-883
  • Peer Reviewed
• [Journal Article] Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by new compound JBIR-23 (2011)
  • Author(s): Ji-Hwan Hwang
  • Journal Title: Cancer letters Volume: 300 Pages: 189-196
  • Peer Reviewed
• [Journal Article] Characteristic methylation profile of CpG island metylater phenotype-negative distal colorectal cancers (2010)
  • Author(s): Byonggu An
  • Journal Title: International journal of cancer Volume: 127 Pages: 2095-2105
  • 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] 悪性胸膜中皮腫におけるYAPがん遺伝子の標的遺伝子検索 (2011)
  • Author(s): 水野鉄也
  • Organizer: 日本肺癌学会総会
  • Place of Presentation: リーガロイヤルホテル大阪
  • Year and Date: 2011-11-04
• [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
• [Presentation] Expression and functional analysis of Hairy Enhancer of Split 1 (HES1) in malignant mesothelioma cell lines (2010)
  • Author(s): 村上秀樹
  • Organizer: The 10^<th> International Conference of the International Mesothelioma Interest Group
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2010-09-02
• [Presentation] 悪性中皮腫細胞株におけるBAP1遺伝子異常の検討
  • Author(s): 石黒 太志
  • Organizer: 日本肺癌学会総会
  • Place of Presentation: 岡山シティミュージアム
• [Remarks]
  • URL: http://www.aichi-med-u.ac.jp/