Elucidation of roles of hemidesmosomal components in skin tumor initiation.

• Project/Area Number: 17K19514
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical structure and function and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Matsumura Hiroyuki 東京医科歯科大学, 難治疾患研究所, 助教 (70581700)
• Research Collaborator: Nishimura Emi K ; Nanba Daisuke ; Liu Nan ; Takada Aki
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 細胞競合 / RAS変異細胞 / ヘミデスモソーム / COL17A1 / 遺伝子改変マウス / RAS変異 / 表皮基底細胞 / 癌遺伝子 / 扁平上皮癌 / ヘムデスモソーム / １７型コラーゲン

Outline of Final Research Achievements

Cell competition is a mechanism in which high fitness cells outcompete as winners and low fitness cells are eliminated from tissues as losers when high fitness cells and low cells coexist. However, it is largely unknown whether RAS mutant cells or hemidesmosomal components by epidermal basal cells are involved in the maintenance of tissue homeostasis through cell competition. In this study, we have generated an experimental system for analysis of in vivo cell competition in epidermal basal cells utilizing genetically modified animals, and verified those phenomena.

Academic Significance and Societal Importance of the Research Achievements

本研究では、遺伝子改変マウスを用いて、今まで全く明らかにされてこなかった、ヘミデスモソーム構成因子が、表皮基底細胞における細胞競合に関与している可能性を示すことができた。この細胞競合現象と組織恒常性維持機構との関係性の全容が解明できれば、皮膚の癌化・老化機構の基本原理の解明や細胞競合を介した新規薬剤開発へ繋がる可能性も高い。これらのことから、学術的・社会的観点からも大変意義深い研究成果であると考えられる。

Research Products

• [Journal Article] Stem cell competition orchestrates skin homeostasis and ageing (2019)
  • Author(s): Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, Geroges-Labouesse E, Nanba D, Nishimura EK
  • Journal Title: Nature Volume: 568(7752) Issue: 7752 Pages: 344-350
  • DOI: 10.1038/s41586-019-1085-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Beclin 1 regulates recycling endosome and is required for skin development in mice (2019)
  • Author(s): Noguchi Saori、Honda Shinya、Saitoh Tatsuya、Matsumura Hiroyuki、Nishimura Emi、Akira Shizuo、Shimizu Shigeomi
  • Journal Title: Communications Biology Volume: 2 Issue: 1 Pages: 37-37
  • DOI: 10.1038/s42003-018-0279-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Stem cell competition orchestrates skin homeostasis and ageing (2019)
  • Author(s): Nan Liu, Hiroyuki Matsumura○, Tomoki Kato, Daisuke Nanba, Emi K. Nishimura
  • Organizer: Japan-Singapore Skin International Conference
  • Int'l Joint Research
• [Presentation] ヘミデスモソーム構成因子による幹細胞競合における役割の解明 (2018)
  • Author(s): 松村 寛行○
  • Organizer: 第8回細胞競合コロキウム
• [Presentation] Epidermal stem cell competition coupled with stem cell division in mammalian epidermis (2018)
  • Author(s): Nan Liu○, Hiroyuki Matsumura, Tomoki Kato, Daisuke Nanba, Emi K. Nishimura
  • Organizer: Keystone Symposia 2019, Cell Competition in Development and Disease
  • Int'l Joint Research
• [Presentation] NUAK2 promote melanoma development by regulating mTOR pathway (2018)
  • Author(s): Namiki T.○, Matsumura H., Yaguchi T., Kawakami Y., Nishimura E., Yokozeki H.
  • Organizer: International Investigative Dermatology (IID) 2018
  • Int'l Joint Research
• [Presentation] 表皮基底細胞の細胞競合におけるヘミデスモソーム構成因子の役割の解明 (2018)
  • Author(s): 松村 寛行○
  • Organizer: 第６回細胞競合領域班会議
• [Presentation] 毛包の老化メカニズム (2018)
  • Author(s): 松村 寛行○
  • Organizer: 第６回皮膚の会
• [Presentation] 毛包の老化メカニズム (2018)
  • Author(s): 松村 寛行○
  • Organizer: 第７回細胞競合コロキウム
• [Presentation] 毛包の老化における好中球エラスターゼの役割の解析 (2018)
  • Author(s): 加藤智起○、松崎健、松村寛行、Nan Liu、村口太一、森永浩伸、西村栄美
  • Organizer: 新学術領域「幹細胞老化と疾患」・「細胞競合」合同若手の会
• [Presentation] 毛包の老化における好中球エラスターゼの役割の解析 (2018)
  • Author(s): 加藤智起、松崎健、松村寛行、Nan Liu、村口太一、森永浩伸、西村栄美
  • Organizer: 新学術領域「幹細胞老化と疾患」・「細胞競合』合同若手の会
• [Presentation] 毛包の老化メカニズム (2018)
  • Author(s): 松村 寛行
  • Organizer: 第７回細胞競合コロキウム
• [Presentation] 毛包の老化メカニズム (2018)
  • Author(s): 松村 寛行
  • Organizer: 第６回皮膚の会
• [Presentation] Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis (2017)
  • Author(s): Hiroyuki Matsumura
  • Organizer: 東京医科歯科大学第2回再生学領域合同セミナー
• [Presentation] Hemidesomosomal components-mediated cell polarity and the cell division axis determine hair follicle stem cell fates during aging (2017)
  • Author(s): Hiroyuki Matsumura, Nan Liu, Daisuke Nanba, Shizuko Ichinose, Aki Takada, Makoto Fukuda, Elisabeth Geroges-laboohouse, Shigeo Ohno, Emi K Nishimura
  • Organizer: 15 th Stem Cell Research Symposium
• [Presentation] Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis (2017)
  • Author(s): Hiroyuki Matsumura, Yasuaki Mohri, Nguyen Thanh Binh, Hironobu Morinaga,Makoto Fukuda, Mayumi Ito, Sotaro Kurata, Jan Hoeijmakers, Emi K. Nishimura
  • Organizer: 3rd International Symposium on Cell Competition, Cell Competition in Development and Cancer
  • Int'l Joint Research
• [Presentation] 表皮基底細胞の細胞競合におけるヘミデスモソーム構成因子の役割の解明 (2017)
  • Author(s): 松村寛行
  • Organizer: 新学術領域細胞競合第３回班会議
• [Presentation] Defective maintenance of hair follicle stem cells through COL17A1 loss orchestrates the hair follicle aging program (2017)
  • Author(s): Hiroyuki Matsumura, Yasuaki Mohri, Nguyen Thanh Binh, Hironobu Morinaga, Makoto Fukuda, Mayumi Ito, Sotaro Kurata, Jan Hoeijmakers, Emi K. Nishimura
  • Organizer: 47th Annual European Society for Dermatological Research (ESDR) Meeting
  • Int'l Joint Research
• [Presentation] Locomotive ability of human keratinocyte stem cells is an intrinsic property for stem cell expansion and epidermal reconstruction (2017)
  • Author(s): D.Nanba, F.Toki, H.Matsumura, H.Toki, E.K.Nishimura
  • Organizer: 47th Annual European Society for Dermatological Research (ESDR) Meeting
  • Int'l Joint Research