Role of PPAR-mediated pathway on induction of anoikis in squamous cell carcinoma

• Project/Area Number: 18592028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: WADA Koichiro Osaka University, 大学院・歯学研究科, 准教授 (90263467)
• Co-Investigator(Kenkyū-buntansha): KAMISAKI Yoshinori 大阪大学, 大学院・歯学研究科, 教授 (40116017)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 核内受容体 / PPAR / 扁平上皮癌 / アノイキス / 浸潤 / Apoptosis / 細胞増殖 / PPARgamma / 高脂肪 / 生活習慣病 / エストロゲン / 扇平上皮癌

Research Abstract

扁平上皮癌における核内受容体PPAR を介した転写制御系の役割を検討したところ、核内受容体PPAR が高発現していること、このPPAR を阻害したところアノイキスとよばれる接着阻害による細胞死がおこり癌細胞の浸潤が有意に抑制されることが明らかになった。この核内受容体PPARを介した転写制御系の下流には様々な細胞機能制御系の分子群が存在することも明らかになった。核内受容体PPAR を制御することにより癌細胞の増殖・浸潤を抑制できることが示唆された。

Research Products

• [Journal Article] Association between angiotensin II type1receptor polymorphisms and the occurrence of nonalcoholic fatty liver disease (2009)
  • Author(s): Yoneda M, Hotta K, Takahashi H, Wada K, Nakajima A
  • Journal Title: Liver International (in press)
  • Peer Reviewed
• [Journal Article] Association of visceral fat accumulation and plasma adiponection with rectal dysplastic aberrant crypt foci in a clinical population (2009)
  • Author(s): Takahashi H, Takayama T, Wada K
  • Journal Title: Cancer Sci 100 Pages: 29-32
  • Peer Reviewed
• [Journal Article] Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway (2009)
  • Author(s): Sugiyama M, Takahashi H, Wada K
  • Journal Title: Int. J. Oncol 34 Pages: 339-344
  • Peer Reviewed
• [Journal Article] Upregulation of S100A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen (2009)
  • Author(s): Inaba H, Hokamura K, Nakano K, Nakajima A, KamisakiY, Ooshima T, Umemura K, Wada K, Amano A
  • Journal Title: FEBS Lett 583 Pages: 128-134
  • Peer Reviewed
• [Journal Article] Adiponectin inhibits colorectal cancer cell growth through theAMPK/mTOR pathway. (2009)
  • Author(s): Sugiyama M, Takahashi H, Hosono K, Endo H, Kato s, Yoneda K, Nozaki Y, Fujita K, Yoneda M, Wada K, et al
  • Journal Title: Int. J. Oncol. 34 Pages: 339-344
  • Peer Reviewed
• [Journal Article] Upregulation of S100 calcium-binding protein A9 is required for induction of smooth musde cell proliferation by a periodontal pathogen. (2009)
  • Author(s): Inaba H, Hokamura K, Nakano K, Nomura R, Katayama K, Nakajima A, Yoshioka H, Taniguchi K, Kamisaki Y, Ooshima T, Umemura K, Murad F, Wada K, Amano A.
  • Journal Title: FEBS Letters 583 Pages: 128-134
  • Peer Reviewed
• [Journal Article] Association of visceral fat accumulation and plasma adiponectin with rectal dysplastic aberrant crypt foci in a clinical population. (2009)
  • Author(s): Takahashi H, Takayama T, Yoneda K, Endo H, Iida H, Sugiyama M, Fujita K, Yoneda M, Iramori M, Abe Y, Saito S, Wada K, et al.
  • Journal Title: Cancer Science 100 Pages: 29-32
  • NAID: 10025141134
  • Peer Reviewed
• [Journal Article] Comparison of the protective effect of N-acetylcysteine by different treatments on rat myocardial ischemia-reperfusion injury (2008)
  • Author(s): Abe M, Takiguchi Y, Ichimura S, Tuchiya K, Wada K
  • Journal Title: J. Pharmacol. Sci. 106 Pages: 571-577
  • NAID: 10024319840
  • Peer Reviewed
• [Journal Article] PPARg suppresses colonic epithelial cell turnover and colon carcinogenesis through inhibition of the beta-catenin/ TCF pathway (2008)
  • Author(s): Fujisawa T, Nakajima A, Fujisawa N, Wada K, et.al.
  • Journal Title: J. Pharmacol. Sci. 106 Pages: 627-638
  • Peer Reviewed
• [Journal Article] Activation of PPARγ suppresses mast cell maturation involved in allergic diseases (2008)
  • Author(s): Tachibana M, Wada K, Kamisaki Y, et al.
  • Journal Title: Allergy 63 Pages: 1136-1147
  • Peer Reviewed
• [Journal Article] Gene Expression Profiling of NASH by Gene Set Enrichment Analysis (2008)
  • Author(s): Yoneda M, Endo H, Tsutsumi S, Aburatani H, Wada K, et al.
  • Journal Title: Hepatol. Res. 38 Pages: 1204-1212
  • Peer Reviewed
• [Journal Article] Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease (2008)
  • Author(s): Fujita K, Nozaki Y, Wada K, et al.
  • Journal Title: Gut 57 Pages: 1583-1591
  • Peer Reviewed
• [Journal Article] Expression of adiponectin receptors, AdipoR1 and R2, in normal colon epithelium and colon cancer tissue (2008)
  • Author(s): Yoneda K, Tomimoto A, Wada K, Nakagama H, Nakajima A.
  • Journal Title: Oncology Reports 20 Pages: 479-483
  • Peer Reviewed
• [Journal Article] Association between PPARgC1A polymorphisms and the occurrence of NAFLD (2008)
  • Author(s): Yoneda M, Nozaki Y, Wada K, Nakajima A, Hosono K.
  • Journal Title: BMC Gastroenterology 8, 27
  • Peer Reviewed
• [Journal Article] Metoformin suppresses intestinal polyp growth in ACP (Min-/+) Mice (2008)
  • Author(s): Tomimoto A, Wada K, Nakagama H, Nakajima A.
  • Journal Title: Cancer Science 99 Pages: 2136-2141
  • Peer Reviewed
• [Journal Article] Inhibition of PPARg activity suppresses pancreatic cancer cell motility (2008)
  • Author(s): Nakajima A, Tomimoto A, Fujita K, Wada K, Nakagama H
  • Journal Title: Cancer Science 99 Pages: 1892-1900
  • Peer Reviewed
• [Journal Article] Nitric oxide plays a crucial role in the development/progression of NASH in the CDAA diet-fed rat model (2008)
  • Author(s): Fujita K, Yoneda M, Wada K, Takahashi H, Nakajima A
  • Journal Title: Alcohol. Clin. Exp. Res. (in press)
  • Peer Reviewed
• [Journal Article] Different effect of acute treatment with rosiglitazone on rat myocardial ischemia/reperfusion injury by administration method (2008)
  • Author(s): Abe M, Takiguchi Y, Wada K
  • Journal Title: Eur J Pharmacol 589 Pages: 215-219
  • Peer Reviewed
• [Journal Article] Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition (2008)
  • Author(s): Fujisawa T, Endo H, Kadowaki T, Wada K, .
  • Journal Title: Gut 57 Pages: 1531-1538
  • Peer Reviewed
• [Journal Article] Inhibition of PPARg promotes tumorigenesis through activation of b-catenin/TCF pathway in the mouse intestine (2008)
  • Author(s): Fujisawa T, Sugiyama M, Wada K,et al.
  • Journal Title: J. Pharmacological Sci. 108 Pages: 535-544
  • Peer Reviewed
• [Journal Article] 内分泌撹乱物質の脂肪蓄積促進作用 (2008)
  • Author(s): 和田孝一郎
  • Journal Title: 日本薬理学雑誌 131 Pages: 310-311
  • NAID: 10024382514
• [Journal Article] Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases. (2008)
  • Author(s): Tachibana M, Wada_K, Katayama K, Kamisaki Y, et al.
  • Journal Title: Allergy 36 Pages: 1136-1147
  • Peer Reviewed
• [Journal Article] Adiponectin suppresses colorectal carcinogenesis under high-fat diet condition. (2008)
  • Author(s): Fujisawa T, Endo H, Watanabe M, Kubota N, Yamauchi T, Kadowaki T, Wada K, et al.
  • Journal Title: Gut 57 Pages: 1531-1538
  • Peer Reviewed
• [Journal Article] Inhibition of peroxisome proliferator-activated receptor gamma activity suppresses pancreatic cancer cell motility. (2008)
  • Author(s): Nakajima A, Tomimoto A, Takahashi H, Ikeda I, Hosono K, Endo H, Yoneda K, Kubota K, Nakajima N, Wada K, et al.
  • Journal Title: Cancer Science 99 Pages: 1892-1890
  • Peer Reviewed
• [Journal Article] Effectiveness of antiplatelet drugs against experimental non- alcoholic fatty liver disease. (2008)
  • Author(s): Fujita K, Nozaki Y, Wada k, Yoneda M, Endo H, et al.
  • Journal Title: Gut 57 Pages: 1583-1591
  • Peer Reviewed
• [Journal Article] Metformin suppresses intestinal polyp growth in ApcMin-/+mice. (2008)
  • Author(s): Tomimoto A, Emdo H, FujisawaT, Takahashi H, Wada K, et al
  • Journal Title: Cancer Science 99 Pages: 2136-2141
  • NAID: 10024012700
  • Peer Reviewed
• [Journal Article] Inhibition of peroxisome proliferator-activated receptor gamma promotes tumorigenesis through activation of beta-catenin/T cell factor (TCF) pathway in the mouse intestine. (2008)
  • Author(s): Fujisawa T, Sugiyama M, Tomimoto A, Wada K, et al.
  • Journal Title: J. Pharmacol. Sci. 108 Pages: 535-544
  • NAID: 130000075870
  • Peer Reviewed
• [Journal Article] Expression of adiponectin receptors, AdipoRl and AdipoR2, in normal colon epithelium and colon cancer tissue. (2008)
  • Author(s): Yoneda K, Tornimoto A, Endo H, Iida H, Sugiyama M, Takahashi H, Mawatari H, Nozaki Y, Fujita K, Yoneda M, Inamori M, Nakajima N, Wada K, et al
  • Journal Title: Oncol. Rep. 20 Pages: 479-483
  • Peer Reviewed
• [Journal Article] Gene expression profiling of non-alcoholic steatohepatitis using gene set enrichment analysis. (2008)
  • Author(s): Yoneda M, Endo H, Mawatari H, Nozaki Y, Fuiita K, Aburatani H, Wada K, et al.
  • Journal Title: Hepatol. Res. 38 Pages: 1204-1202
  • NAID: 10023920679
  • Peer Reviewed
• [Journal Article] Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD). (2008)
  • Author(s): Yoneda M, Hotta K. Nozaki Y, Endo H, Uchiyama T, Maeyama s, Wada K, et al.
  • Journal Title: BMC Gastroenterol. 8 Pages: 27-27
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor gamma (PPARgamma) suppresses colonic epithelial cell turnover and colon carcinogenesis through inhibition of the beta-catenin/T cell factor (TCF) pathway. (2008)
  • Author(s): Fujisawa T, Nakajima A, Takahashi H, IKeda I, Tomimoto A, Yonemitsu K, Nakajima N, Kud C, Wada K, et al.
  • Journal Title: J. Pharmacol. Sci. 106 Pages: 627-638
  • Peer Reviewed
• [Journal Article] 神経幹細胞の分化・増殖における脂質メディエーターの役割 (2008)
  • Author(s): 和田孝一郎
  • Journal Title: 大阪大学歯学雑誌 52 Pages: 19-21
  • NAID: 10026061968
• [Journal Article] Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer (2007)
  • Author(s): Ihara A, Wada K, Yoneda M, Fujisawa N, Nakajima A, et al.
  • Journal Title: J. Pharmacol. Sci. 103 Pages: 24-32
  • NAID: 130000074876
  • Peer Reviewed
• [Journal Article] Hypoadiponectinemia plays a crucial role in the development of NAFLD in patients with type 2 diabetes mellitus independent of visceral adipose tissue (2007)
  • Author(s): Yoneda M, Iwasaki T, Wada K, Terauchi Y, Nakajima A
  • Journal Title: Alcohol. Clin. Exp. Res. 31
  • Peer Reviewed
• [Journal Article] Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma (2007)
  • Author(s): Ishida H, Wada K, Masuda T, Okura M, Sano Y, Nakajima A, Kogo M, Kamisaki Y
  • Journal Title: Cancer Sci. 98 Pages: 636-643
  • Peer Reviewed
• [Journal Article] Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats (2007)
  • Author(s): Fujita K, Yoneda M, Wada K, et al.
  • Journal Title: Dig. Dis. Sci. 52 Pages: 3455-3464
  • Peer Reviewed
• [Journal Article] 5-Aminosalicylic acid given in the remission stage of colitis suppresses colitis-associated cancer in a mouse colitis model (2007)
  • Author(s): Ikeda I, Tomimoto A, Wada K, et al.
  • Journal Title: Clin. Cancer Res. 13 Pages: 6527-6531
  • Peer Reviewed
• [Journal Article] Life style-related diseases of digestive system : from molecular mechanisms to therapeutic strategies (2007)
  • Author(s): Nakajima A, Wada K.
  • Journal Title: J.Pharmacol.Sci. 105 Pages: 127-128
  • Peer Reviewed
• [Journal Article] Endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome (2007)
  • Author(s): Wada K, et al.
  • Journal Title: J. Pharmacol. Sci. 105 Pages: 133-137
  • Peer Reviewed
• [Journal Article] Gene expression in nonalcoholic steatohepatitis patients and treatment strategies (2007)
  • Author(s): Yoneda M, Endo H, Aburatani H, Wada K, et al.
  • Journal Title: J. Pharmacol.Sci. 105 Pages: 151-156
  • Peer Reviewed
• [Journal Article] PPAR と神経疾患 (2007)
  • Author(s): 和田孝一郎, 上崎善規
  • Journal Title: 医学のあゆみ 220 Pages: 111-116
• [Journal Article] PPARによる遺伝子治療 (2007)
  • Author(s): 形山和史, 和田孝一郎, 真弓忠範
  • Journal Title: 医学のあゆみ 220 Pages: 117-123
• [Journal Article] Critical role of estrogen receptor on anoikis and invasion of squamous cell carcinoma. (2007)
  • Author(s): Ishida H, Wada K, et. al.
  • Journal Title: Cancer Science 98 Pages: 636-643
  • Peer Reviewed
• [Journal Article] 5-Aminosalicylic acid given in the remission stage of colitis suppresses colitis-associated cancer in a mouse colitis model. (2007)
  • Author(s): Ikeda I, Tomimoto A, Wada K., et. al.
  • Journal Title: Clinical Cancer Research 13 Pages: 6527-6531
  • Peer Reviewed
• [Journal Article] Life style-related diseases of the digestive system: Endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. (2007)
  • Author(s): Wada K, et. al.
  • Journal Title: Journal of Pharmacological Sciences 105 Pages: 133-137
  • NAID: 10024316045
  • Peer Reviewed
• [Journal Article] Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of novalcoholic steatohepatitis in rats. (2007)
  • Author(s): Fujita K, Yoneda M, Wada K, et. al.
  • Journal Title: Digestive Diseases and Sciences 52 Pages: 3455-3464
  • Peer Reviewed
• [Journal Article] Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer (2007)
  • Author(s): Ihara A, Wada K, et al.
  • Journal Title: Journal of Pharmacological Sciences 103・1 Pages: 24-32
  • NAID: 130000074876
• [Journal Article] PPARと神経疾患 (2007)
  • Author(s): 和田孝一郎, 上崎善規
  • Journal Title: 医学のあゆみ 220・1 Pages: 111-116
• [Journal Article] PPARg-mediated regulation of neural stem cell proliferation and differentiation (2006)
  • Author(s): Wada K, Nakajima A, Katayama K, Kudo C, Shibuya A, Tachibana M, Kamisaki Y, Mayumi T, Kadowaki T, Blumberg RS
  • Journal Title: J. Biol. Chem. 281 Pages: 12673-12681
  • Peer Reviewed
• [Journal Article] Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation (2006)
  • Author(s): Wada K, Arita M, Nakajima A, Kudo C, Kamisaki Y, Serhan CN
  • Journal Title: FASEB J. 20 Pages: 1785-1792
  • Peer Reviewed
• [Journal Article] Inhibition of PPARg activity in esophageal carcinoma cells results in a drastic decrease of invasive properties (2006)
  • Author(s): Takahashi H, Schaefer K, Saubermann LJ, Wada K, et al.
  • Journal Title: Cancer Sci. 97 Pages: 854-860
  • Peer Reviewed
• [Journal Article] 生活習慣病の治療戦略 (2006)
  • Author(s): 中山貢一, 和田孝一郎
  • Journal Title: 日本薬理学雑誌 128:207
• [Journal Article] PPARγリガンドを用いた非アルコール性脂肪性肝炎 (NASH) の治療戦略 (2006)
  • Author(s): 米田正人, 藤田浩司, 中島淳, 和田孝一郎
  • Journal Title: 日薬理誌 128 Pages: 235-238
  • NAID: 10018811451
• [Journal Article] Peroxisome proliferator-activated receptor γ-mediated regulation of neural stem cell proliferation and differentiation (2006)
  • Author(s): Wada K, Nakajima A, et al.
  • Journal Title: Journal of Biological Chemistry 281・18 Pages: 12673-12681
• [Journal Article] Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation (2006)
  • Author(s): Wada K, Arita M, et al.
  • Journal Title: The FASEB journal 20 Pages: 1785-1792
• [Journal Article] Inhibition of peroxisome proliferators-activated receptor gamma activity in esophageal carcinoma cells results in a drastic decrease of invasive properties (2006)
  • Author(s): Takahashi H, Fujita K, et al.
  • Journal Title: Cancer Science 97・9 Pages: 854-860
• [Journal Article] 『生活習慣病の治療戦略』PPARγリガンドを用いた非アルコール性脂肪性肝炎 (NASH)の治療戦略 (2006)
  • Author(s): 米田正人, 藤田浩司, 中島淳, 和田孝一郎
  • Journal Title: 日本薬理学雑誌 128・4 Pages: 235-238
• [Presentation] Involvement of P. gingivalis on the development of human aortic aneurysm. (2009)
  • Author(s): Wada K etal.
  • Organizer: 第82回日本薬理学会年会(シンポジウム)
  • Place of Presentation: 横浜
• [Presentation] Mcl-l as a target for the therapy of squamous cell carcinoma (2009)
  • Author(s): Nagata M, Wada K, et al.
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Endocrine disrupting compounds, bisphenols, accelerate adipocyte differentiation. (2009)
  • Author(s): Nakanishi M, Wada K, Sakuma s, Nakajima A, Kamisaki Y, Fujimoto Y.
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Mcl-lは口腔扁平上皮癌の細胞増殖を制御する (2008)
  • Author(s): 永田雅英, 和田孝一郎, 草山守生, 飯田征二, 大倉正也, 古郷幹彦, 上崎善規
  • Organizer: 第107回大阪大学歯学会例会 第55回総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-12-03
• [Presentation] 脂肪細胞分化におけるロイコトリエンB_4の役割 (2008)
  • Author(s): 平田佳永, 和田孝一郎, 高田健治, 上崎善規
  • Organizer: 第107回大阪大学歯学会例会 第55回総会
  • Place of Presentation: 大阪
  • Year and Date: 2008-12-03
• [Presentation] 扁平上皮癌におけるMyeloid cell leukemia-l発言抑制による抗癌剤の作用増強 (2008)
  • Author(s): 永田雅英, 和田孝一郎, 草山守夫, 大倉正也, 古郷幹彦, 上崎善規
  • Organizer: 第114回日本薬理学会近畿部会
  • Place of Presentation: 神戸
  • Year and Date: 2008-11-14
• [Presentation] 脂肪細胞分化におけるロイコトリエンの役割 (2008)
  • Author(s): 平田佳永, 和田孝一郎, 上崎善規
  • Organizer: 第50回歯科基礎医学会学術大会ならびに総会
  • Place of Presentation: 東京
• [Presentation] 口腔扁平上皮癌細胞の増殖におけるMyeloid cell leukemia-1の役割 (2008)
  • Author(s): 永田雅英, 和田孝一郎, 草山守生, 古郷幹彦, 上崎善規
  • Organizer: 第50回歯科基礎医学会学術大会ならびに総会
  • Place of Presentation: 東京
• [Presentation] Involvement of P.gingivalis on the development of human aortic aneurysm
  • Author(s): 和田孝一郎
  • Organizer: 第82 回日本薬理学会年会シンポジウム
  • Place of Presentation: 横浜
• [Presentation] Endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome
  • Author(s): 和田孝一郎
  • Organizer: 第80 日本薬理学会年会シンポジウム
  • Place of Presentation: 名古屋
• [Book] 核内受容体型転写制御因子PPARγと新規タンパクMonad による細胞増殖分化死の制御機構生命歯科医学のカッティング・エッジ (2008)
  • Author(s): 和田孝一郎, 佐伯万騎男, 上崎善規
  • Publisher: 大阪大学出版会
• [Book] PPAR と神経疾患(各疾患への最新アプローチ動向)PPAR と疾患 (2008)
  • Author(s): 和田孝一郎, 上崎善規
  • Publisher: 医歯薬出版
• [Book] PPARと疾患(別冊医学のあゆみ) (2008)
  • Author(s): 和田孝一郎(野出孝一 編)
  • Total Pages: 130
  • Publisher: 医歯薬出版
• [Remarks]
  • URL: http://www.dma.jim.osaka-u.ac.jp/kg-portal/aspi/RX0011D.asp?UNO=12686&page=