Regulation of metabolic shift by drs tumor suppressor gene

• Project/Area Number: 23590457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TAMBE Yukihiro 滋賀医科大学, 医学部, 助教 (50283560)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 癌 / 代謝 / 癌抑制遺伝子 / メタボローム / グルコース代謝 / drs / 乳酸脱水素酵素 / エネルギー代謝 / ワールブルグ効果

Research Abstract

The drs gene is the tumor suppressor gene that regulates apoptosis and autophagy in cancer cells. However, its physiologic function in normal cells is unclear. In this study, by using drs knockout (KO) mouse embryonic fibroblast cells, we found that genetic loss of drs induces the metabolic shift toward aerobic glycolysis by increasing the expression and activity of lactose dehydrogenase (LDH). It is suggested that drs participates in the regulation of glucose metabolism and down-regulation of drs during tumorigenesis is involved in the induction of Warburg effect in human cancers. We also found that the induction of drs into KO cells and the treatment of cancer cells with LDH inhibitor could suppress the metabolic shift and the malignant transformation. Further investigations will contribute toward developing a new anticancer therapy.

Research Products

• [Journal Article] Female-specific rectal carcinogenesis in cyclin D1b transgenic mice. (2014)
  • Author(s): Tambe, Y., Kim, C. J., Munkaisho, K., Sugihara, H., Isono, T., Sonoda, H., Shimizu, T., Kondoh, G., Inoue, H.
  • Journal Title: Carcinogenesis Volume: 35 Issue: 1 Pages: 227-236
  • DOI: 10.1093/carcin/bgt293
  • Peer Reviewed
• [Journal Article] Suppression of viral replication by drs tumor suppressor via mTOR dependent pathway (2012)
  • Author(s): Tambe, Y., et al
  • Journal Title: Cancer Letters Volume: 314 Issue: 1 Pages: 82-91
  • DOI: 10.1016/j.canlet.2011.09.015
  • Peer Reviewed
• [Journal Article] Suppression of viral replication by drs tumor suppressor via mTOR dependent pathway. (2012)
  • Author(s): Tambe Y, Okuyama N, Nakagawa T, Muramoto A, Hasebe M, Chano T, Inoue H.
  • Journal Title: Cancer Lett. Volume: 314 Pages: 82-91
  • Peer Reviewed
• [Journal Article] Opposite regulation of epitnelial-to mesenchymal transition and cell invasiveness by periostin between prostate and bladder cance cells (2011)
  • Author(s): Kim, C.J., et al
  • Journal Title: Int.J.One. Volume: 38 Pages: 1759-1766
  • DOI: 10.3892/ijo.2011.997
  • Peer Reviewed
• [Presentation] Molecular mechanism of female specific rectal carcinogenesis in cyclin D1b transgenic mice (2013)
  • Author(s): Yukihiro Tambe, Chul Jang Kim, Ken ichi Mukaisho, Hiroyuki Sugihara, Hirokazu Inoue
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-05
• [Presentation] Molecular mechanism of the regulation of Warburg effect by the drs tumor suppressor gene (2013)
  • Author(s): Yukihiro Tambe, Hirokazu Inoue
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-05
• [Presentation] Molecular mechanism of female specific rectal carcinogenesis in cyclin D1b transgenic mice (2013)
  • Author(s): Chul Jang Kim, Yukihiro Tambe, Ken ichi Mukaisho, Hiroyuki Sugihara, Hirokazu Inoue
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-05
• [Presentation] drs がん抑制遺伝子による Warburg 効果制御の分子機構 (2013)
  • Author(s): 旦部幸博、井上寛一
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Cyclin D1b トランスジェニックマウスにおける雌特異的直腸腫瘍 発生の分子機構の解析 (2013)
  • Author(s): 金哲將、旦部幸博、向所賢一、杉原洋行、井上寛一
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Cyclin D1bトランスジェニックマウスにおける雌特異的直腸腫瘍発生の分子機構 (2013)
  • Author(s): 旦部幸博、金哲將、向所賢一、杉原洋行、井上寛一
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Drs tumor suppressor gene is involved in regulation of Warburg effect (2012)
  • Author(s): Masahiro Hasebe, Akitsugu Yamamoto, Yukihiro Tambe, Hirokazu Inoue
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] Female specific development of rectal cancers via serrated pathway in cyclin D1b transgenic mice (2012)
  • Author(s): Yukihiro Tambe, Chul Jang Kim, Ken ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Hiromichi Sonoda, Tomoharu Shimizu, Gen Kondoh, Hirokazu Inoue
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-01
• [Presentation] In vivo and in vitro oncogenic potential of human cyclin D1b variant (2012)
  • Author(s): Hirokazu Inoue, Yukihiro Tambe, Ken ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Gen Kondoh, Chul Jang Kim
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] The drs tumor suppressor gene is involved in regulation of Warburg effect (2012)
  • Author(s): Yukihiro Tambe, Hirokazu Inoue
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] Studies on the oncogenic potential of rectal tumor developed in cyclic D1b transgenic mice (2012)
  • Author(s): Chul Jang Kim, Yukihiro Tambe, Ken ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Gen Kondoh, Hirokazu Inoue
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] The drs tumor suppressor gene is involved in regulation of Warburg effect (2012)
  • Author(s): Yukihiro Tambe, Hirokazu Inoue.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Studies on the oncogenic potential of rectal tumor developed in cyclic D1b transgenic mice (2012)
  • Author(s): Chul Jang Kim, Yukihiro Tambe, Ken-ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Gen Kondoh, Hirokazu Inoue.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] In vivo and in vitro oncogenic potential of human cyclin D1b variant (2012)
  • Author(s): Hirokazu Inoue, Yukihiro Tambe, Ken-ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Gen Kondoh, Chul Jang Kim
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Female-specific development of rectal cancers via serrated pathway in cyclin D1b-transgenic mice (2012)
  • Author(s): Yukihiro Tambe, Chul Jang Kim, Ken-ichi Mukaisho, Hiroyuki Sugihara, Takahiro Isono, Hiromichi Sonoda, Tomoharu Shimizu, Gen Kondoh, Hirokazu Inoue
  • Organizer: 第35回分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] Role of the drs tumor suppressor in regulation of energy metabolism (2011)
  • Author(s): Yukihiro Tambe, Hirokazu Inoue
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Role of cyclin D1b variant in rectal tumorigenesis (2011)
  • Author(s): Chul Jang Kim, Yukihiro Tambe, Takahiro Isono, Ken ichi Mukaisho, Hiroyuki Sugihara, Gen Kondoh, Hirokazu Inoue
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Roll of the drs tumor suppressor in regulation of energy metabolism (2011)
  • Author(s): Yukihiro Tambe, Hirokazu Inoue.
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
• [Remarks]
  • URL: http://www.shigamed.ac.jp/~hqmicro/
• [Remarks] 滋賀医大病理学講座微生物感染症学部門
  • URL: http://www.shiga-med.ac.jp/~hqmicro/
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~hqmicro/