Search for YAP/TAZ-regulating factors

• Project/Area Number: 15K07052
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: University of Occupational and Environmental Health, Japan (2016-2017); Kyushu University (2015)
• Principal Investigator: HIKASA Hiroki 産業医科大学, 医学部, 講師 (40596839)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Hippo経路 / YAP/TAZ / 活性制御 / Hippo 経路 / 腫瘍化 / 組織再生 / YAP/TAZ制御機構 / 腫瘍化と再生 / Hippo経路の分子探索 / YAP/TAZ活性化機構

Outline of Final Research Achievements

In order to elucidate the molecular basis of Hippo pathway that is a tumor-suppressive signal, we performed cell-based high throughput screening and mass spectrometry to search for genes and compounds which control or functionally interact with Hippo pathway. We successfully identified several compounds including ivermectin and its derivative milbemycin D as mediators of Hippo pathway and applied for patents. In addition, we revealed that Hippo pathway drives a tumor- suppressive pathway that is dependent on Lin28B, a microRNA regulator and an oncoprotein.

Research Products

• [Journal Article] Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells. (2017)
  • Author(s): Kitajima S, Lee KL, Hikasa H, Sun W, Huang RY, Yang H, Matsunaga S, Yamaguchi T, Araki M, Kato H, Poellinger L
  • Journal Title: Oncotarget. Volume: 8 Issue: 70 Pages: 114481-114494
  • DOI: 10.18632/oncotarget.23010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Merlin/NF2-Lin28B-let7 is a novel tumor-suppressive pathway that is cell density-dependent and Hippo-independent (2016)
  • Author(s): Hikasa H., Sekido Y. and Suzuki A.
  • Journal Title: Cell reports Volume: 14 Issue: 12 Pages: 2950-2961
  • DOI: 10.1016/j.celrep.2016.02.075
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dysregulated YAP1/TAZ and TGF signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice (2015)
  • Author(s): Nishio, M., Sugimachi, K., Goto, H., Wang, J., Morikawa, T., Miyachi, Y., Takano, Y., Hikasa, H., Itoh, T., Suzuki, S.O., Kurihara, H., Aishima, S., Leask, A., Sasaki, T., Nakano, T., Nishina, H., Nishikawa, Y., Sekido, Y., Nakao, K., Shin-ya, K., Mimori, K. and Suzuki, A.
  • Journal Title: PNAS Volume: 113 Issue: 1 Pages: 71-80
  • DOI: 10.1073/pnas.1517188113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Hippo経路エフェクターYAP/TAZを制御する因子の検索 (2017)
  • Author(s): 日笠弘基
  • Organizer: 第４０回日本分子生物学会年会
• [Presentation] Merlin regulates the biogenesis via Lin28B suppression in a cell density-dependent manner. (2015)
  • Author(s): Hikasa H., Sekido Y. and Suzuki A
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Patent(Industrial Property Rights)] がん遺伝子産物YAP1/TAZ機能調節剤 (2017)
  • Inventor(s): 日笠 弘基
  • Industrial Property Rights Holder: 日笠 弘基
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017