Global analysis of cancer stem cell-specific phosphorylation of basic amino acids for application to cancer treatment

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659188
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: KUNIYASU Hiroki 奈良県立医科大学, 医学科, 教授 (00253055)
• Co-Investigator(Kenkyū-buntansha): OHMORI Hitoshi 奈良県立医科大学, 医学科, 博士研究員 (80213875)
• Project Period (FY): 2011 – 2012
• Keywords: 塩基性アミノ酸 / リン酸化アミノ酸 / がん幹細胞 / 大腸癌 / リン酸化酵素

Research Abstract

Phosphorylation of basic amino acids were an old knowledge; however, it was hardly examined from their marked lability. We found the free phosphorylated basic amino acids were increased in stem cell-enriched cancer population. Especially, phosphoarginine inhibited pyruvate kinase activity, which induced aerobic glycolysis. Inhibition of the aerobic glycolysis and induction of oxidative phosphorylation decreased stemness of cancer cells. Thus, phosphoarginine might be associated with the energy production of cancer stem cells and stemness maintenance. We also examined the effect of phosphorylation of histone lysine residue on the epigenetics. Histone lysine phosphorylation did not show a simple inhibition of acetylation or methylation of the lysine residue. Histone lysine phosphorylation might induce a transitional status to acetylation or methylation of the lysine residue.

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] 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(3) Pages: 741-751
• [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] 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] 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(6) Pages: 1165-71
• [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(1) Pages: 73-80
• [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): L u o Y, Ohmori H, Fujii K, Chihara Y, Maruyama S, Kuniyasu H
  • Journal Title: Urol Oncol-Semin Ori Volume: 30 Pages: 306-313
• [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 Gastroentero Volume: l 47(10) Pages: 1073-83
• [Journal Article] Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer (2012)
  • Author(s): Shimomoto T, Ohmori H, Luo Y, C h i h a r a Y, Denda A, Sasahira T, Tatsumoto N, Fujii K, Kuniyasu H
  • Journal Title: Clin Exp Metasta Volume: 29(8) Pages: 915-925
• [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] 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(10) Pages: 3246-53
• [Journal Article] Evaluation of metastatic potential of prostate cancer (2011)
  • Author(s): Chihara Y, Fujimoto K, Hirao Y, Kuniyasu H
  • Journal Title: Oncol Rev Volume: 5 Pages: 103-107
• [Journal Article] The roles of HMGB1 related angiogenesis and lymphangiogenesis in oral cancer. (2011)
  • Author(s): Sasahira T, Yamamoto K, Kurihara M, Bhawal UK, Chihara Y, Kirita T, Kuniyasu H
  • Journal Title: Oncol Rev Volume: 5 Pages: 49-55
• [Journal Article] Non-histone nuclear factor HMGB1 as a target in colorectal cancer (2011)
  • Author(s): Ohmori H, Luo Y, Kuniyasu H
  • Journal Title: Expert Opin Ther Tar Volume: 15(2) Pages: 183-193
• [Journal Article] Downregulation of runt-related transcription factor 3 (RUNX3) associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland (2011)
  • Author(s): Sasahira T, Kurihara M, Yamamoto K, Bhawal UK, Kirita T, Kuniyasu H
  • Journal Title: Cancer Sci Volume: 102(2) Pages: 492-497
• [Journal Article] In vitro enhanced differentiation of neural networks in ES gut-like organ from mouse ES cells by a 5-HT4-receptor activation (2011)
  • Author(s): Takaki M, Misawa H, Matsuyoshi, H,Kawahara I, Goto K, Zhang GX, Obata K, Kuniyasu H
  • Journal Title: Biochem Biophys Res Commun Volume: 406(4) Pages: 529-533
• [Journal Article] Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells (2011)
  • Author(s): L u o Y, Ohmori H, Shimomoto T, Fujii K, Sasahira T, Chihara Y, Kuniyasu H
  • Journal Title: Pathobiology Volume: 78(5) Pages: 285-290
• [Journal Article] Basic helix-loop-helix transcription factor DEC1 negatively regulates CyclinD1 (2011)
  • Author(s): Bhawal UK, Sato F, Arakawa Y, Fujimoto K, Kawamoto T, Tanimoto K, Ito Y, Sasahira T, Sakurai T, Kobayashi M, Kashima I, Kajima H, Kuniyasu H, Abiko Y, Kato Y, Sato S
  • Journal Title: J Pathol Volume: 224(3) Pages: 420-429
• [Journal Article] Determinants of the epithelial-muscle axis on embryonic stem cell-derived gut-like structures (2010)
  • Author(s): Luo Y, Takaki M, Misawa H, Matsuyoshi H, Sasahira T, Chihara Y, Fujii K, Ohmori H, Kuniyasu H
  • Journal Title: Pathobiology Volume: 77(5) Pages: 253-259
• [Journal Article] A 5-HT4-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult (2010)
  • Author(s): Matsuyoshi H, Kuniyasu H, Okumura M, Misawa H, Katsui R, Zhang GX, Obata K, Takaki M
  • Journal Title: Neurogastroenterol Motil Volume: 22(7) Pages: 806-814
• [Journal Article] Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma
  • 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
• [Journal Article] Diagnostic markers of urothelial cancer based on DNA methylation analysis
  • Author(s): Chihara Y, Kanai Y, Fujimoto H, Sugano K, Kawashima K, Liang G, Jones PA, Fujimoto K, Kuniyasu H, Hirao Y
  • Journal Title: BMC Cancer
• [Journal Article] Clinically observed taste disorder-related peripheral mechanism in an anticancer drug, S-1 administered rats
  • Author(s): Aoki K, Obata K, Kurihara M, Kuniyasu H,Kirita T, Takaki M
  • Journal Title: Int J Clin Oncol
• [Journal Article] AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer
  • Author(s): Sasaki T, Kuniyasu H, Luo Y, Kitayoshi M, Tanabe E, Kato D, Shinya S, Fujii K, Ohmori H, Yamashita Y
  • Journal Title: Pathobiol
• [Presentation] Effect of intermittent calorie restriction on cancer stem cells (2013)
  • Author(s): Luo Y, Kitadai Y, Chihara Y, Fujiwara R, Fujimoto K, Kuniyasu H
  • Organizer: 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington
  • Year and Date: 20130406-10
• [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] 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
  • Year and Date: 20120331-0404
• [Presentation] 高血糖の大腸癌肝転移に及ぼす影響 (2012)
  • 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: 20120118-19
• [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
• [Presentation] トランス脂肪酸であるエライジン酸の大腸癌への影響 (2011)
  • Author(s): 國安弘基、羅 奕、栗原 都、笹平智則、千原良友、傳田阿由美
  • Organizer: 第26回発癌病理研究会、研究会8
  • Place of Presentation: 札幌市
  • Year and Date: 20110829-31
• [Presentation] 脂肪酸の癌転移への影響 (2011)
  • Author(s): 國安弘基
  • Organizer: 第20回日本癌病態治療研究会
  • Place of Presentation: 東京都
  • Year and Date: 20110617-18
• [Presentation] HMGB1 affects plasma amino acid profiles in colon carcinogenesis (2011)
  • Author(s): Luo Y, Yoneda J, Ohmori H, Shimbo K, Eto S, Fujii K, Sasahira T, Chihara Y, Kuniyasu H
  • Organizer: 102nd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Florida
  • Year and Date: 20110402-06
• [Presentation] Cellular and tissue injury by nano particles (2011)
  • Author(s): Fujiwara R, Kanaoka K, Luo Y, Kuniyasu H
  • Organizer: 21st Hiroshima Cancer Seminar International Symposium
  • Place of Presentation: Hiroshima
  • Year and Date: 2011-11-06