幹細胞特異的塩基性アミノ酸リン酸化の網羅的解析と治療への応用

2012 Fiscal Year Annual Research Report

• Project/Area Number: 23659188
• Research Institution: Nara Medical University
• Principal Investigator: 國安 弘基 奈良県立医科大学, 医学部, 教授 (00253055)
• Co-Investigator(Kenkyū-buntansha): 大森 斉 奈良県立医科大学, 医学部, 研究員 (80213875)
• Keywords: リン酸化アルギニン / 解糖系 / 酸化的リン酸化 / 癌幹細胞

Research Abstract

塩基性アミノ酸リン酸化が癌幹細胞に果たす役割を検討するため、リン酸化アルギニン(pAgr)を用いて、大腸癌細胞株におけるその効果を検討した。CT26マウス大腸癌細胞をpAgrにより処理すると、濃度依存性にpyruvate Kinase活性が低下した。CT26細胞では、PKM2が主に発現しており、PKM1の発現はごく低レベルである。pyruvate Kinase活性の手化に伴い、乳酸発酵による乳酸の生成が増大した。一方、ミトコンドリアにおけるATP産生は低下し、同時にROSの産生も減少した。さらに、pAgr処理によりADHL陽性癌幹細胞数は増加した。このようにpAgrにより、癌細胞にaerobic glycoysisが亢進し、stemnessの増大が誘導される可能性が示唆された。

Research Products

• [Journal Article] Trks are novel oncogenes involved in the induction of neovascularization, tumor progression, and nodal metastasis in oral squamous cell carcinoma (2013)
  • Author(s): Sasahira T, Ueda N, Yamamoto K, Bhawal UK, Kurihara M, Kirita T, Kuniyasu H
  • Journal Title: Clin Exp Metasta Volume: 30 Pages: 165-176
• [Journal Article] In vivo imaging of enteric neurogenesis in the deep tissue of mouse small intestine (2013)
  • Author(s): Goto K, Kawahara I, Luo Y, Obata K, Misawa H, Ishikawa T, Kuniyasu H, Nabekura J, Takaki M
  • Journal Title: Pros One Volume: 8(1) Pages: e54814
• [Journal Article] Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma (2013)
  • Author(s): Kurihara M, Kirita T, Sasahira T, Ohmori H, Matsushima S, Yamamoto K, Bosserhoff AK, Kuniyasu H
  • Journal Title: Br J Cancer Volume: 108(7) Pages: 1460-9
• [Journal Article] High mobility group box 1 released from necrotic cells enhances regrowth and metastasis of cancer cells that have survived chemotherapy. (2013)
  • Author(s): Luo Y, Chihara Y, Fujimoto K, Sasahira T, Kuwada M, Fujiwara R, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Eur J Cancer Volume: 49 Pages: 741-751
  • DOI: 10.1016/j.ejca.2012.09.016
  • Peer Reviewed
• [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma. (2013)
  • Author(s): Sasahira T, Ueda N, Kurihara M, Matsushima S, Ohmori H, Fujii K, Bhawal UK, Yamamoto K, Kirita T, Kuniyasu H
  • Journal Title: Hum Pathol Volume: in press Pages: in press
  • DOI: pii: S0046-8177(12)00360-7. 10.1016/j.humpath
  • Peer Reviewed
• [Journal Article] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer (2013)
  • Author(s): Sasaki T, Kuniyasu H, Luo Y, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y
  • Journal Title: Pathobiology Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Multiple roles of angiotensin in colorectal cancer (2012)
  • Author(s): Kuniyasu H
  • Journal Title: World J Clin Oncol Volume: 3(12) Pages: 150-4
• [Journal Article] The comparison of effects of a selective 5-HT reuptake inhibitor versus a 5-HT-4 receptor agonist on in vivo neurogenesis at the rectal anasotomosis in rats (2012)
  • Author(s): Kawahara I, Kuniyasu H, Matsuyoshi H, Goto K, Obata K, Misawa H, Fujii H, Takaki M
  • Journal Title: Am J Physiol Gastroenterol Liver Volume: 302 Pages: G588-G597
• [Journal Article] Downregulation of miR-126 induces angiogenesis and lymphangiogenesis and targets VEGF-A in oral cancer (2012)
  • Author(s): Sasahira T, Kurihara M, Bhawal UK, Ueda N, Yamamoto K, Kirita T, Kuniyasu H
  • Journal Title: Br J Cancer Volume: 107(4) Pages: 700-6
• [Journal Article] Significance of epithelial growth factor in the epithelial-mesenchymal transition of human gallbladder cancer cells. (2012)
  • Author(s): Sasaki T, Kuniyasu H*, Luo Y, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y.
  • Journal Title: Cancer Sci Volume: 103 Pages: 1165-71
  • DOI: 10.1111/j.1349-7006.2012.02264.x
  • Peer Reviewed
• [Journal Article] Involvement of HMGB1 and RAGE in IL-1β-induced gingival inflammation. (2012)
  • Author(s): Ito Y, Bhawal UK*, Sasahira T, Toyama T, Sato T, Matsuda D, Nishikiori H, Kobayashi M, Sugiyama M, Hamada N, Arakawa H, Kuniyasu H
  • Journal Title: Arch Oral Biol Volume: 57 Pages: 73-80
  • DOI: 10.1016/j.archoralbio.2011.08.001
  • Peer Reviewed
• [Journal Article] High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer (2012)
  • Author(s): Luo Y, Ohmori H, Fujii K, Chihara Y, Maruyama S, Kuniyasu H
  • Journal Title: Urol Oncol-Semin Ori Volume: 30 Pages: 306-313
  • DOI: 10.1016/j.urolonc.2010.05.001
  • Peer Reviewed
• [Journal Article] Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet (2012)
  • Author(s): Shimomoto T, Luo Y, Ohmori H, Chihara Y, Sasahira T, Fujii K, Kuniyasu H
  • Journal Title: J Gastroenterol Volume: 47 Pages: 1073-83
  • DOI: 10.1007/s00535-012-0572-5
  • Peer Reviewed
• [Journal Article] Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer. (2012)
  • Author(s): Shimomoto T, Ohmori H, Luo Y, Chihara Y, Denda A, Sasahira T, Tatsumoto N, Fujii K, Kuniyasu H
  • Journal Title: Clin Exp Metasta Volume: 29 Pages: 915-925
  • DOI: 10.1007/s10585-012-9480-6.
  • Peer Reviewed
• [Journal Article] IL-1β-mediated upregulation of DEC1 in Akt/HIF-1α-dependent pathway. (2012)
  • Author(s): Bhawal UK, Sato F, Sasahira T, Ito Y, Kuniyasu H, Kajima H, Abiko Y.
  • Journal Title: J Cell Biochem Volume: 113 Pages: 3246-53
  • DOI: 10.1002/jcb.24205.
  • Peer Reviewed
• [Presentation] 間欠的カロリー制限のがん幹細胞への影響 (2013)
  • Author(s): 羅 奕、千原良友、笹平智則、桑田正臣、栗原 都、國安弘基
  • Organizer: 「個体レベルでのがん研究支援活動」ワークショップ2013
  • Place of Presentation: 大津市
  • Year and Date: 20130206-07
• [Presentation] 高血糖の大腸癌肝転移に及ぼす影響 (2013)
  • Author(s): 羅 奕、千原良友、下元貴澄、大森 斉、藤井 澄、國安弘基
  • Organizer: 「個体レベルでのがん研究支援活動」ワークショップ2012
  • Place of Presentation: 大津市
  • Year and Date: 20130118-20130119
• [Presentation] 大腸がんにおける宿主代謝への影響 (2012)
  • Author(s): 國安弘基、羅 奕、栗原 都、笹平智則、千原良友、藤井 澄、大森 斉
  • Organizer: 第27 回発癌病理研究会、シンポジウム5
  • Place of Presentation: 伊豆市
  • Year and Date: 20120828-20120830
• [Presentation] 担がん状態における宿主エネルギー代謝の変化 (2012)
  • Author(s): 國安弘基
  • Organizer: 2012年分子病理学セミナー「新しい病理学を創る」
  • Place of Presentation: 周防大島町
  • Year and Date: 20120727-20120728
  • Invited
• [Presentation] Angiotensin in colorectal cancer metastasis (2012)
  • Author(s): Luo Y, Chihara Y, Ohmori H, Fujii K, Yoshikawa M, Kuwata M, Fujimoto K, Hirao Y, Kitadai Y, Kuniyasu H
  • Organizer: 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Chicago, USA
  • Year and Date: 20120401-20120404
• [Presentation] 脂肪酸のがん幹細胞への影響 (2012)
  • Author(s): 國安弘基
  • Organizer: 第6回臨床アミノ酸研究会「がんとアミノ酸」
  • Place of Presentation: 東京都
  • Year and Date: 2012-12-15
• [Book] Significance of angiotensin in metastasis of colon cancer (2012)
  • Author(s): Kuniyasu H
  • Total Pages: 215
  • Publisher: Research Media, Kerala, India