Analysis of human samples for developing a novel therapy that target the Warburg effect

• Project/Area Number: 25430163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• 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): 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) ; 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん / 代謝 / ワールブルグ効果 / 解糖系 / PKM / スプライシング

Outline of Final Research Achievements

It is widely known that cancer cells have lower rates of TCA cycle and oxidative phosphorylation, but less is known about its significance. Here we analyzed human samples for metabolites levels of tumor and corresponding non-cancerous tissues by CE-MS. Lung tumor and normal lung tissue showed differential responses to ischemia in terms of their lactate levels. Our results may be a first report observing the Warburg effect of human patients.

Research Products

• [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA (2015)
  • Author(s): Hayashi K, Momoi Y , Tanuma N, Kishimoto A, Ogoh H, Kato H, Suzuki M, Sakamoto Y, Inoue Y, Nomura M, Kiyonari H, Sakayori M, Fukamachi K, Kakugawa Y, Yamashita Y, Ito S, Sato I, Suzuki A, Nishio M, Suganuma M, Watanabe T, and Shima H
  • Journal Title: Oncogene Volume: 印刷中 Issue: 35 Pages: 4647-55
  • DOI: 10.1038/onc.2014.398
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sialidase NEU3 contributes neoplastic potential on colon cancer cells as a key modulator of gangliosides by regulating Wnt signaling. (2015)
  • Author(s): Takahashi K, Hosono M, Sato I, Hata K, Wada T, Yamaguchi K, Nitta K, Shima H, Miyagi T.
  • Journal Title: Int J Cancer Volume: published online Issue: 7 Pages: 00-00
  • DOI: 10.1002/ijc.29527
  • Peer Reviewed
• [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis. (2015)
  • Author(s): Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
  • Journal Title: Cancer Lett. Volume: 365 Issue: 2 Pages: 223-228
  • DOI: 10.1016/j.canlet.2015.05.022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis. (2015)
  • Author(s): Kiyoto Shiga, Kohta Takahashi, Ikuro Sato, Kengo Kato, Shigeru Saijo, Setsuko Moriya, Masahiro Hosono, Taeko Miyagi
  • Journal Title: Cancer Science Volume: 106 Issue: 11 Pages: 1544-1553
  • DOI: 10.1111/cas.12810
  • Peer Reviewed
• [Journal Article] Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum. (2015)
  • Author(s): Hata K, Tochigi T, Sato I, Kawamura S, Shiozaki K, Wada T, Takahashi K, Moriya S, Yamaguchi K, Hosono M, Miyagi T.
  • Journal Title: Cancer Sci Volume: 106 Issue: 4 Pages: 383-389
  • DOI: 10.1111/cas.12627
  • Peer Reviewed
• [Journal Article] Anterior gradient 2 is correlated with EGFR mutation in lung adenocarcinoma tissues. (2015)
  • Author(s): Narumi S, Miki Y, Hata S, Ebina M, Saito M, Mori K, Kobayashi M, Suzuki T, Iwabuchi E, Sato I, Maemondo M, Endo C, Inoue A, Kondo T, Yamada-Okabe H, Ichinose M, Sasano H.
  • Journal Title: Int J Biol Markers. Volume: 30(2) Issue: 2 Pages: 234-242
  • DOI: 10.5301/jbm.5000131
  • Peer Reviewed
• [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA (2015)
  • Author(s): Hayashi K、ほか20名
  • Journal Title: Oncogene Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Sialidase NEU3 contributes neoplastic potential on colon cancer cells as a key modulator of gangliosides by regulating Wnt signaling. (2015)
  • Author(s): Takahashi K、ほか8名
  • Journal Title: Int J Cancer Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Circulating miR-483-3p and miR-is h21 ighly expressed in plasma of pancreatic cancer. (2015)
  • Author(s): Abue M、ほか10名
  • Journal Title: Int J Oncol Volume: 46 Pages: 539-47
  • Peer Reviewed
• [Journal Article] Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. (2014)
  • Author(s): Abue, M., Yokoyama, M., Shibuya, R., Tamai, K., Yamaguchi, K., Sato, I., Tanaka, N., Hamada, S., Shimosegawa, T., Sugamura, K., Satoh, K.
  • Journal Title: Int J Oncol Volume: 10 Issue: 2 Pages: 1-9
  • DOI: 10.3892/ijo.2014.2743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of Pyruvate kinase M2 in transcriptional regulation and epithelial-mesenchymal transition (2014)
  • Author(s): Hamabe A、ほか13名
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111 Pages: 15526-31
  • Peer Reviewed
• [Journal Article] Gastric-type endocervical glandular neoplasms associated with aberrant p16 expression and K-RAS gene mutation in Peutz-Jeghers syndrom (2014)
  • Author(s): Ito S、ほか5名
  • Journal Title: Pathol Int. Volume: 64 Pages: 283-8
  • Peer Reviewed
• [Presentation] 紫外線誘導皮膚がんにおいて、PP6はがん抑制遺伝子として働く (2015)
  • Author(s): 黒沢是之、後藤孝浩、田沼延公、加藤浩之、佐藤郁郎、伊藤しげみ、島礼、館正弘
  • Organizer: 第24回 日本形成外科学会基礎学術集会
  • Place of Presentation: 岩手県民会館（岩手県・盛岡市）
  • Year and Date: 2015-10-08
• [Presentation] 皮膚Ppp6c欠損マウスは、UVB誘導皮膚扁平上皮発がんに高感受性となる (2015)
  • Author(s): 加藤浩之、田沼延公、三浦康、角川陽一郎、椎葉健一、山下洋二、林克剛、野村美有樹、佐藤郁郎、伊藤しげみ、渡邊利雄、島礼
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Regulation of isoform-expression of pyruvate kinase M (PKM) during cellular differentiation and senescence (2014)
  • Author(s): Nomura M、ほか8名
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-26
• [Presentation] Characterization of mice expressing a single isoform of pyruvate kinase M (2014)
  • Author(s): Sakamoto Y、ほか8名
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-26
• [Presentation] 単一のピルビン酸キナーゼMアイソフォームを発現するマウスの解析 (2014)
  • Author(s): 坂本良美、ほか３名
  • Organizer: 第２回 がんと代謝研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-11
• [Presentation] Pyruvate kinase type M2(PKM2)is involved in human gastric cancer development. (2013)
  • Author(s): Takeharu Shiroki,Nobuhiro Tanuma,Ikuro Sato,Nobuyuki Tanaka,Kazuo Sugamura,Kennichi Satoh
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] ノックインモデルを用いた、ピルビン酸キナーゼM（PKM）アイソフォームの機能解析 (2013)
  • Author(s): 坂本良美、渡邊利雄、野村美有樹、山下洋二、椎葉健一、佐藤郁郎、佐藤雅美、島礼、田沼延公
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Generation of knock-in mice to dissect isoform-specific roles for each splicing isoform of pyruvate kinase M in vivo (2013)
  • Author(s): 松本祥子、坂本良美、野村美有樹、田中遼大、盛田麻美、伊藤しげみ、椎葉健一、野村栄樹、片倉隆一、山下洋二、佐藤郁郎、渡邊利雄、島礼、田沼延公
  • Organizer: 第36回分子生物学会
  • Place of Presentation: 神戸