The role of ER stress response for overcoming oral cancer

• Project/Area Number: 25870562
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology; Functional basic dentistry
• Research Institution: University of Miyazaki
• Principal Investigator: HISAE Kadowaki 宮崎大学, 医学部, 助教 (40568200)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 小胞体ストレス / シグナル伝達 / 口腔がん

Outline of Final Research Achievements

The ER is the organelle in which proteins form their functional tertiary structure. Dysfunction of the ER leads to the accumulation of misfolded proteins in the ER. Cells possess ER quality control systems to remove these proteins and thereby survive. On the other hand, tumor cells are challenged by microenvironments such as hypoxia and hypoglycemia, which lead to the induction of ER stress. It is well known that ER stress-induced survival signaling is activated during tumor cell growth. However, the molecular mechanism underlying this process remains unclear. Is this project, we focused on oral cancer in which significance of ER stress signaling has never been evaluated and aimed at therapeutic approaches.
Our results from the experiments using anticancer agent which induces ER stress-mediated cell death revealed that ER stress is involved in cancer.

Research Products

• [Journal Article] Role of Apoptosis Signal-regulating Kinase 1 (ASK1) as an activator of the GAPDH-Siah1 Stress-Signaling Cascade. (2015)
  • Author(s): Tristan C.A., Ramos A., Shahani N., Emiliani F.E., Nakajima H., Noeh C.C., Kato Y., Takeuchi T., Noguchi T., Kadowaki H., Sedlak T.W., Ishizuka K., Ichijo H., Sawa, A.
  • Journal Title: The Journal of Biological Chemistry Volume: 290 Issue: 1 Pages: 56-64
  • DOI: 10.1074/jbc.m114.596205
  • Peer Reviewed / Open Access
• [Journal Article] SOD1 as a molecular switch for initiating the homeostatic ER stress respouse under zinc deficiency. (2013)
  • Author(s): Homma, K., Fujisawa. T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H., Matsuzawa, A., Naguro, I., and Ichijo, H.
  • Journal Title: Molecular Cell Volume: 52 Issue: 1 Pages: 75-86
  • DOI: 10.1016/j.molcel.2013.08.038
  • Peer Reviewed
• [Journal Article] Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreatic s cell exhaustion (2013)
  • Author(s): Yamaguchi, K., Takeda, K., Kadowaki, H., Ueda, I., Namba, Y., Ouchi, Y. Nishitoh, H. and Ichijo, H.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1830 Issue: 6 Pages: 3656-3663
  • DOI: 10.1016/j.bbagen.2013.01.029
  • Peer Reviewed
• [Journal Article] Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease (2013)
  • Author(s): Kadowaki, H. Nishitoh, H.
  • Journal Title: Genes Volume: 4 Issue: 3 Pages: 306-333
  • DOI: 10.3390/genes4030306
  • Peer Reviewed
• [Presentation] 新規小胞体品質管理機構の分子メカニズム (2015)
  • Author(s): 門脇寿枝
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
  • Invited
• [Presentation] 小胞体ストレス誘導性翻訳時分解の分子機構の解明 (2014)
  • Author(s): 門脇寿枝、西頭英起
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] The molecular mechanism of novel ER quality control system (2014)
  • Author(s): 門脇寿枝、西頭英起
  • Organizer: 第66回日本細胞生物学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] Derlinファミリーを介した小胞体品質管理システム (2014)
  • Author(s): 門脇寿枝、西頭英起
  • Organizer: 日本生化学会九州支部
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] 小胞体ストレス誘導性翻訳時分解の分子機構の解明 (2013)
  • Author(s): 門脇寿枝、一條秀憲、西頭英起
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜