Development of novel therapy targeting the Warburg effect of cancer

2012 Fiscal Year Final Research Report

• Project/Area Number: 23650629
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: Miyagi Cancer Center Research Institute
• Principal Investigator: SATO Ikuro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), ティッシュバンクセンター, センター長 (50225918)
• Co-Investigator(Kenkyū-buntansha): ITO Shigemi 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (80600006) ; TANUMA Nobuhiro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 主任研究員 (40333645)
• Project Period (FY): 2011 – 2012
• Keywords: 代謝 / 解糖系 / ワールブルグ効果 / PKM / スプライシング

Research Abstract

A glycolytic enzyme, pyruvate kinase M (PKM), has been suggested to play important roles in altered metabolism in cancer cells. In this study, we analyzed splicing regulation of the PKM gene in tumor. Analysis using clinical specimens revealed that pre-mRNA splicing of PKM gene switches from M1- to M2-type in most case of various human cancers. In addition, we developed a reporter gene enabling us to detect PKM conversion in living cells.

Research Products

• [Journal Article] H:Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas (2012)
  • Author(s): Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, Katakura R, Yamashita Y, Sato M, Tanuma N, Shima H
  • Journal Title: Oncol Rep. Volume: 28(3) Pages: 931-6
  • DOI: doi:10.3892/
• [Journal Article] Case report of Mammary Analog Secretory Carcinoma of the parotid gland (2012)
  • Author(s): Ito S, Ishida E, Skalova A, Matsuura K, Kumamoto H, Sato I
  • Journal Title: Pathol Int. Volume: 62(2) Pages: 149-52
  • DOI: doi:10.1111/j.1440-1827.2011.02759.x.
• [Journal Article] Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling (2012)
  • Author(s): Kawamura S, Sato I, Wada T, Yamaguchi K, Li Y, Li D, Zhao X, Ueno S, Aoki H, Tochigi T, Kuwahara M, Kitamura T, Takahashi K, Moriya S, Miyagi T
  • Journal Title: Cell Death Differ. Volume: 19(1) Pages: 170-9
• [Journal Article] Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase (2012)
  • Author(s): Yamaguchi K, Shiozaki K, Moriya S, Koseki K, Wada T, Tateno H, Sato I, Asano M, Iwakura Y, Miyagi T
  • Journal Title: PLoS One. Volume: 7(7)
• [Journal Article] 発がんにおけるPKMスイッチ-意義と分子機構 (2012)
  • Author(s): 田沼延公
  • Journal Title: 実験医学 特集「がんと代謝」 Volume: Vol. 30、No. 15 Pages: 42-47
• [Journal Article] DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression (2011)
  • Author(s): Katagiri C, Masuda K, Nomura M, Tanoue K, Fujita S, Yamashita Y, Katakura R, Shiiba K, Nomura E, Sato M, Tanuma N, Shima H
  • Journal Title: Mol Cell Biochem. Volume: 352(1-2) Pages: 155-62
  • DOI: doi:10.1007/s11010-011-0749-x.
• [Presentation] PKMスイッチ不可能なマウスモデルの開発 (2013)
  • Author(s): 田沼延公
  • Organizer: 日本癌学会 がん代謝シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-01-17
• [Presentation] 炎症性脳アミロイド血管症の一例 (2012)
  • Author(s): 山下洋二、鈴木博義、伊藤しげみ、佐藤郁郎、片倉隆一
  • Organizer: 第19回東北脳神経病理研究会
  • Place of Presentation: 風島
  • Year and Date: 2012-11-17
• [Presentation] A mouse model incapable of switching PKM isoforms (2012)
  • Author(s): 田沼延公、渡邊利雄、野村美有樹、佐藤郁郎、椎葉健一、山下洋二、佐藤雅美、島礼
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20