Investigation into mechanisms of cancer aggressiveness by epithelial cells undergoing EMT

• Project/Area Number: 24390419
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: University of Yamanashi
• Principal Investigator: SAITOH Masao 山梨大学, 大学院総合研究部, 教授 (90345041)
• Research Collaborator: ENDO Kaori ; SAKAMOTO Kei ; ISHII Hiroki ; HOSHI Yuta ; FUKAGAWA Akihiko ; FURUYA Satoshi ; MIYAZAWA Keiji ; KAWASAKI Tomonori
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: EMT / TGF-beta / がん細胞 / シグナル伝達 / 上皮間葉転換 / 悪性形質 / がん / 浸潤 / 分子マーカー / TGF-β

Outline of Final Research Achievements

I performed experiments based on "Investigation into mechanisms of cancer aggressiveness by epithelial cells undergoing EMT". Using DNA microarray analyses, I explored several molecular marker proteins which are specifically expressed in epithelial cells undergoing EMT. I found that the marker proteins, Ret and Pai2, are expressed in aggressive cancer cells, whereas the marker protein (ITGA3) is in the most aggressive cells. However, ITGA3 was also expressed in fibroblast or mesenchymal cells in cancer microenvironment, as determined by immunohistochemical analyses. These findings have been published in articles and the details,includind gene Z, will be investigated by me and my collaborators.

Research Products

• [Journal Article] STAT3 integrates cooperative Ras and TGF-β signals that induce Snail expression (2015)
  • Author(s): Masao Saitoh, Kaori Endo, Satoshi Furuya, Munetaka Minami, Akira Fukasawa, Takeshi Imamura, Keiji Miyazawa
  • Journal Title: Oncogene Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The epithelial-mesenchymal transition is regulated at the post-transcriptional levels by TGF-β signaling during tumor progression (2015)
  • Author(s): Masao Saitoh
  • Journal Title: Cancer Science Volume: 印刷中 Issue: 5 Pages: 481-488
  • DOI: 10.1111/cas.12630
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Basolateral BMP signaling in polarized epithelial cells (2013)
  • Author(s): Saitoh M, Shirakihara T, Fukasawa A, Horiguchi K, Sakamoto K, Sugiya H, Beppu H, Fujita Y, Morita I, Miyazono K, Miyazawa K.
  • Journal Title: PLoS One Volume: 13 Issue: 5 Pages: 1-10
  • DOI: 10.1371/journal.pone.0062659
  • Peer Reviewed / Open Access
• [Journal Article] Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β (2013)
  • Author(s): Motizuki M, Isogaya K, Miyake K, Ikushima H, Kubota T, Miyazono K, Saitoh M, Miyazawa K.
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 26 Pages: 18911-18922
  • DOI: 10.1074/jbc.m113.480996
  • Peer Reviewed / Open Access
• [Journal Article] Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. (2013)
  • Author(s): Shirakihara T, Kawasaki T, Fukagawa A, Semba K, Sakai R, Miyazono K, Miyazawa K, Saitoh M.
  • Journal Title: Cancer Science Volume: 104 Issue: 9 Pages: 1189-1197
  • DOI: 10.1111/cas.12220
  • Peer Reviewed
• [Journal Article] Basolateral BMP signaling in polarized epithelial cells (2013)
  • Author(s): M Saitoh, et al
  • Journal Title: PLOSONE Volume: (印刷中)
  • Peer Reviewed
• [Presentation] Roles of STAT3 in Snail induction by the synergism between Ras and TGF-β (2015)
  • Author(s): Masao Saitoh, Satoshi Furuya, Keiji Miyazawa
  • Organizer: TGF-beta meeting
  • Place of Presentation: 筑波大学（茨城県・つくば市）
  • Year and Date: 2015-01-11 – 2015-01-13
• [Presentation] δEF1associates with DNMT1 and maintains DNA methylation of the E-cadherin promoter in breast cancer cells (2014)
  • Author(s): Masao Saitoh, Akihiko Fukagawa, Hiroki Ishii, Keiji Miyazawa
  • Organizer: 第７３回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] FGF-2 accelerates TGF-beta-induced EMT (2013)
  • Author(s): Masao Saitoh
  • Organizer: AACR
  • Place of Presentation: Omni SanDiego (アメリカ)
  • Year and Date: 2013-01-21
• [Presentation] Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. (2013)
  • Author(s): 齋藤正夫
  • Organizer: 第５５回歯科基礎医学会総会
  • Place of Presentation: 岡山コンベンションセンター（ 岡山県岡山市）
• [Presentation] Identification of integrin α3 as a molecular marker of cells undergoing epithelial-mesenchymal transition and of cancer cells with aggressive phenotypes. (2013)
  • Author(s): Masao Saitoh
  • Organizer: 6th EMT meeting
  • Place of Presentation: Hotel Melia (Alicante, Spain)
• [Presentation] role of TGF-b superfamily signals in EMT and epithelial cell polarity (2013)
  • Author(s): Masao Saitoh
  • Organizer: 第８６回生化学会総会
  • Place of Presentation: 横浜コンチネンタルホテル（ 神奈川県横浜市）
  • Invited
• [Presentation] Identification of integrin α3 as a molecular marker of cells undergoing EMT and of cancer cells with aggressive phenotypes (2013)
  • Author(s): Masao Saitoh
  • Organizer: FASEB meeting
  • Place of Presentation: The Steamboat Grand Resort (Steamboat SpringsSteamboat, USA)
• [Presentation] TGF-b誘導性EMTと癌微小環境 (2013)
  • Author(s): 斉藤正夫
  • Organizer: 第45回結合組織学会 第60回マトリックス研究会大会 合同大会
  • Place of Presentation: 和歌山県立医科大学（ 和歌山県和歌山市）
  • Invited
• [Presentation] Roles of TGF-b superfamily signals in EMT and cancer progression (2012)
  • Author(s): Masao Saitoh
  • Organizer: 日本癌学会総会
  • Place of Presentation: 札幌文化会館(北海道)(招待講演)
  • Year and Date: 2012-09-21
• [Presentation] TGF-b誘導性EMTの分子機構 (2012)
  • Author(s): Masao Saitoh
  • Organizer: 歯科基礎医学会総会
  • Place of Presentation: 奥羽大学(福島県)
  • Year and Date: 2012-09-15
• [Presentation] Role of BMP signaling in TGF-b mediated EMT (2012)
  • Author(s): Masao Saitoh
  • Organizer: TGF-beta meeting
  • Place of Presentation: Leiden大学(オランダ)
  • Year and Date: 2012-08-30
• [Remarks]
  • URL: http://sangaku.yamanashi.ac.jp/SearchResearsher/contenrs/EF8E5AD567D62505.html