Elucidation of the EMT-mediated invasion and metastasis mechanisms of cancer stem cells in the head and neck cancer microenvironment

• Project/Area Number: 17K11398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Nara Medical University
• Principal Investigator: OTA ICHIRO 奈良県立医科大学, 医学部, 講師 (00326323)
• Co-Investigator(Kenkyū-buntansha): 高橋 昭久 群馬大学, 重粒子線医学推進機構, 教授 (60275336)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん幹細胞 / 微小環境 / 浸潤・転移 / EMT / 頭頸部外科学

Outline of Final Research Achievements

The importance of the microenvironment surrounding cancer cells has received much attention. The susceptibility of cancer to invasion and metastasis is closely related not only to the cancer cells themselves, but also to the interactions between cancer cells and their microenvironment. We have found that the Wnt signaling pathway induces EMT (Epithelial-Mesenchymal Transition) through Snail to acquire the invasion and metastatic potential of cancer cells. This current study suggested that EMT is a key factor in cancer invasion and metastasis as well as an important regulator of cancer stem cells. Furthermore, identification of cancer stem cells in the microenvironment and analysis of their activation in head and neck cancer cells suggested that EMT was enhanced in the cancer microenvironment and the cancer invasiveness was also enhanced.

Academic Significance and Societal Importance of the Research Achievements

Wntシグナル伝達経路がSnailを介してEMTを誘導することで、MT1-MMPおよびMT2-MMPを活性化させるとともに、がん細胞の浸潤・転移能を獲得させることを示した。さらに、頭頸部がん細胞においていかにしてがん微小環境がEMTを誘導し、がん幹細胞を活性化させ浸潤・転移を促しているかを、in vitroおよびin vivoのレベルで分子生物学的手法および独自の浸潤・転移モデルを用いて解明の糸口を見出した。今後、その経路の分子標的薬の開発により、一層の治療効果が期待できる。

Research Products

• [Presentation] Snail-induced EMT promotes the properties of cancer stem cells in head and neck cancer cells in vitro and in vivo (2018)
  • Author(s): Ichiro Ota, Takashi Masui, et al.
  • Organizer: IFHNOS 2018
  • Int'l Joint Research
• [Presentation] The mechanism of cancer invasion and metastasis through EMT signaling in head and neck cancer (2017)
  • Author(s): Ota I, Kimura T, Masui T, Yook JI, Mikami S, Uemura H, Kitahara T
  • Organizer: 5th Congress of ASHNO
  • Int'l Joint Research