Roles of NF-kappaB activation in gastrointestinal tumorigenesis

• Project/Area Number: 22300317
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: Yokohama City University
• Principal Investigator: MAEDA Shin 横浜市立大学, 医学研究科, 教授 (40415956)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Motoyuki 東京大学, 医学部附属病院, 助教 (90518945) ; IJICHI Hideaki 東京大学, 医学部附属病院, 助教 (70463841)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 癌 / 動物 / 炎症

Research Abstract

It is thought that NF-kappaB activation is one of the important signal transduction systems for inflammation-related carcinogenesis. We analyzed the relationship between the NF-kappaB activation and gastrointestinal cancer development.The activation was observed in many gastrointestinal cancers. Using in vitro culture system and mouse model, NF-kappaB activation was an important malignant factor for gastric and pancreatic cancers, suggesting that inhibition of NF-kappaB activity may become adrug target.

Research Products

• [Journal Article] Promotion of DNA repair bynuclear IKKβ phosphorylation of ATM in response togenotoxic stimuli (2013)
  • Author(s): Sakamoto K, Hikiba Y, Nakagawa H, Hirata Y, Hayakawa Y, Kinoshita H, Nakata W,Sakitani K, Takahashi R, Akanuma M, Kamata H, Maeda S
  • Journal Title: Oncogene Volume: 32 Pages: 1854-62
  • Peer Reviewed
• [Journal Article] Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumongenesis. (2013)
  • Author(s): Kinoshita H, et al.
  • Journal Title: PLoS One Volume: 12 Issue: 4 Pages: 1-10
  • DOI: 10.1371/journal.pone.0060914
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase-1inhibitor as a potent therapeutic drug for the treatment of gastric cancer (2012)
  • Author(s): Hayakawa Y, Hirata Y, Sakitani K, Nakagawa H, Nakata W, Kinoshita H, Takahashi R, Takeda K, Ichijo H, Maeda S, Koike K
  • Journal Title: Cancer Sci Volume: 103 Pages: 2181-5
  • Peer Reviewed
• [Journal Article] Anti-tumor activity of the proteasome inhibitor bortezomibin gastric cancer (2012)
  • Author(s): Nakata W, Hayakawa Y, Nakagawa H, Sakamoto K, Kinoshita H, Takahashi R,HirataY, Maeda S, Koike K
  • Journal Title: Int J Oncol Volume: 39 Pages: 1529-36
  • Peer Reviewed
• [Journal Article] Colon cancer-derived factors activate NF-κB in myeloid cells viaTLR2 to linkinflammation and tumorigenesis (2012)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Nakagawa H, Hirata Y, Hayakawa Y, Akanuma M
  • Journal Title: Mol Med Report Volume: 4 Pages: 1083-8
  • Peer Reviewed
• [Journal Article] Promotion of DNA repair by nuclear IKKβ phosphorylation of ATM in response to genotoxic stimuli. (2012)
  • Author(s): Kei Sakamoto, et al.
  • Journal Title: Oncogene Volume: 32 Issue: 14 Pages: 1854-1862
  • DOI: 10.1038/onc.2012.192
  • Peer Reviewed
• [Journal Article] Altered Composition of Fatty Acids Exacerbates Hepatotumorigenesis duringActivation of the Phosphatidylinositol 3-kinase Pathway (2011)
  • Author(s): Kudo Y, Tanaka Y, Tateishi K, Yamamoto K, Yamamoto S, Mohri D, IsomuraY,Seto M, Nakagawa H, Asaoka Y, Tada M, Ohta M, Ijichi H, Hirata Y, Otsuka M,Ikenoue T, Maeda S, Shiina S, Yoshida H, Nakajima O, Kanai F, Omata M, Koike K
  • Journal Title: J Hepatol. J Hepatol Volume: 55 Pages: 1400-8
  • Peer Reviewed
• [Journal Article] Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma (2011)
  • Author(s): Ijichi H, Chytil A, Gorska AE, Aakre ME, Bierie B, Tada M, Mohri D, Miyabayashi K, Asaoka Y, Maeda S, Ikenoue T, Tateishi K, Wright CV, Koike K, Omata M, Moses HL
  • Journal Title: J Clin Invest Volume: 121 Pages: 4106-17
  • Peer Reviewed
• [Journal Article] Gastric Cancer Risk According to the Distribution ofIntestinal Metaplasia and Neutrophil Infiltration (2011)
  • Author(s): Sakitani K, Hirata Y, Watabe H, Yamada A, Sugimoto T, Yamaji Y, Yoshida H,Maeda S, Omata M, Koike K
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Pages: 1570-5
  • Peer Reviewed
• [Journal Article] Apoptosissignal-regulating kinase 1 inhibits hepatocarcinogenesisby controlling thetumor-suppressing function of stress-activated mitogen-activated protein kinase (2011)
  • Author(s): Nakagawa H, Hirata Y, Takeda K, Hayakawa Y, Sato T, Kinoshita H, Sakamoto K, Nakata W, Hikiba Y, Omata M,Yoshida H, Koike K, Ichijo H, Maeda S
  • Journal Title: Hepatology Volume: 54 Pages: 185-95
  • Peer Reviewed
• [Journal Article] Reducedexpression of RAS protein activator like-1 in gastric cancer (2011)
  • Author(s): Seto M, Ohta M, Ikenoue T, Sugimoto T, Asaoka Y, Tada M, Mohri D, Kudo Y,Ijichi H, Tateishi K, Otsuka M, Hirata Y, Maeda S, Koike K, Omata M
  • Journal Title: Int J Cancer Volume: 128 Pages: 1293-302
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase 1 and cyclin D1compose a positive feedback loop contributing to tumor growth in gastric cancer. (2011)
  • Author(s): Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Kinoshita H, NakataW, Takahashi R, Tateishi K, Tada M, Akanuma M, Yoshida H, Takeda K, Ichijo H,Omata M, Maeda S, KoikeK
  • Journal Title: Proc Natl Acad Sci U S A Volume: 8 Pages: 780-5
  • Peer Reviewed
• [Journal Article] Gastric Cancer Risk According to the Distribution of Intestinal Metaplasia and Neutrophil Infiltration (2011)
  • Author(s): Sakitani K, Hirata Y, Watabe H, Yamada A, Sugimoto T, Yamaji Y, Yoshida H, Maeda S, Omata M, Koike K
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Pages: 1570-75
  • Peer Reviewed
• [Journal Article] Altered composition of fatty acids exacerbates hepatotumorigenesis during activation ofthe phosphatidylinositol 3-kinase pathway (2011)
  • Author(s): Kudo Y, Tanaka Y, Tateishi K, Yamamoto K, Yamamoto S, Mohri D, Isomura Y, SetoM, Nakagawa H, Asaoka Y, Tada M, Ohta M, Ijichi H, Hirata Y, Otsuka M, Ikenoue T, Maeda S, Shiina S, Yoshida H, Nakajima O, Kanai F, Omata M, Koike K
  • Journal Title: J Hepatol Volume: 55 Pages: 1400-8
  • Peer Reviewed
• [Journal Article] Apoptosissignal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling thetumor-suppressing function of stress-activated mitogen-activated protein kinase (2011)
  • Author(s): Nakagawa H, Hirata Y, Takeda K, Hayakawa Y, Sato T, Kinoshita H, Sakamoto K, Nakata W, Hikiba Y, Omata M, Yoshida H, Koike K, Ichijo H, Maeda S
  • Journal Title: Hepatology Volume: 54 Pages: 185-95
  • Peer Reviewed
• [Journal Article] Anti-tumor activity of the proteasome inhibitor bortezomibin gastric cancer (2011)
  • Author(s): Nakata W, Hayakawa Y, Nakagawa H, Sakamoto K, Kinoshita H, Takahashi R, Hirata Y, Maeda S, Koike K
  • Journal Title: Int J Oncol Volume: 39 Pages: 1529-36
  • Peer Reviewed
• [Journal Article] Colon cancer-derived factors activate NF-kB in myeloid cells via TLR2 to linkinflammation and tumorigenesis (2011)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Nakagawa H, Hirata Y, Hayakawa Y, Akanuma M
  • Journal Title: Mol Med Report Volume: 4 Pages: 1083-88
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase 1 and cyclin D1 compose apositive feedback loop contributing to tumor growth in gastric cancer (2011)
  • Author(s): Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Kinoshita H, Nakata W, Takahashi R, Tateishi K, Tada M, Akanuma M, Yoshida H, Takeda K, Ichijo H, Omata M, Maeda S, Koike K.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108 Pages: 780-785
  • Peer Reviewed
• [Journal Article] IkappaB kinase beta regulates gastric carcinogenesis via IL-1α expression (2010)
  • Author(s): Sakamoto K, Hikiba Y, Nakagawa H, Hayakawa Y, Yanai A, Akanuma M, Ogura K, Yoshida H, Hirata Y, Kaestner KH, Omata M, Maeda S
  • Journal Title: Gastroenterology Volume: 139 Pages: 226-38
  • Peer Reviewed
• [Presentation] Nuclear IKKβ phosphorylates ATM in response to genotoxic stimuli (2012)
  • Author(s): Sakamoto K, Hikiba Y, Hirata Y, Akanuma M, Kamata H, Maeda S
  • Organizer: 第34回日本分子生物学会年会, ワークショップ
  • Place of Presentation: パシフィコ横浜(神奈川県
  • Year and Date: 2012-12-15
• [Presentation] IRF1 欠損はヘリコバクター関連胃発癌に促進的に関与する (2012)
  • Author(s): 芝田 渉,安崎 弘晃,前田愼
  • Organizer: 第54回日本消化器病学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2012-10-10
• [Presentation] KRAS もしくは BRAF 変異がもたらす抗癌剤負可時の大腸癌細胞のシグナル伝達の解析 (2012)
  • Author(s): 坂本啓,平田喜裕,前田愼
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-19
• [Presentation] Ask1 Plays a Critical Role in H.pylori-induced Gastric Inflammation and Metaplasia (2012)
  • Author(s): Hayakawa Y,Hirata Y, Nakagawa H, Sakitani K , Kinoshita H, Takahashi R,Nakata W, Sakamoto K, Akanuma M, Maeda S, Koike K
  • Organizer: DIGESTIVE DISEASE WEEK (DDW)
  • Place of Presentation: San Diego.USA
  • Year and Date: 2012-05-20
• [Presentation] Nuclear IKK β Phosphorylates ATM in Response to Genotoxic Stimuli (2012)
  • Author(s): Sakamoto K,Hikiba Y, Hayakawa Y,Hirata Y, Akanuma M, Maeda S
  • Organizer: Which Helps Cancer Cell to Survive DNA Damage
  • Place of Presentation: San Diego.USA.
  • Year and Date: 2012-05-19
• [Presentation] Loss ofIRF Signaling Contributes to the Development of Helicobacter Associated Gastric Carcinogenesis in Vivo (2012)
  • Author(s): Shibata W, Yasuzaki H, Kubushiro Y,Hotta C, Tamura T, Maeda S
  • Organizer: DIGESTIVE DISEASE WEEK (DDW)
  • Place of Presentation: San Diego.USA
  • Year and Date: 2012-05-19
• [Presentation] Nuclear IKK β phosphorylates ATM in response to genotoxic stimuli, which promotes DNA reqair (2011)
  • Author(s): Sakamoto K, Hikiba Y, Hirata Y, Akanuma M, Kamata H, Maeda S
  • Organizer: The 34^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-12-15
• [Presentation] Inflammation-and stress-related signaling pathways in gastriccarcinogenesis (2011)
  • Author(s): Maeda S
  • Organizer: International Scientific Coordination Network (ISCN) Groupement de Recherche (GDRI)
  • Place of Presentation: Montpellier.FRANCE
  • Year and Date: 2011-11-24
• [Presentation] Inflammation-and stress-related signaling pathways in gastric carciogenesis (2011)
  • Author(s): Maeda S
  • Organizer: International Scientific Coordination Network(ISCN)Groupement de Recherche(GDRI)
  • Place of Presentation: フランス:Montpellier(招待講演)
  • Year and Date: 2011-11-24
• [Presentation] Interleukin-6(IL-6)Plays an Important Role in Epithelial-Stromal Interactionand Promotes Gastric Tumorigenesis (2011)
  • Author(s): Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R, Nakata W, Sakitani K, Hikiba Akanuma M, Maeda S, Koike K
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: アメリカ:Chicago
  • Year and Date: 2011-11-19
• [Presentation] DNA 損傷により惹起される核内 IKKβ による ATM リン酸化と DNA 修復促進 (2011)
  • Author(s): 坂本啓, 早河翼, 中田和智子, 平田喜裕, 前田愼
  • Organizer: 第70回日本癌学会学術総
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-05
• [Presentation] ヘリコバクターピロリ感染による発癌と炎症の役割 (2011)
  • Author(s): 前田愼
  • Organizer: 第97回日本消化器病学会総会 シンポジウム 7 (ヘリコバクターピロリ感染症の徹底検証)
  • Place of Presentation: 京王プラザホテル(東京都).
  • Year and Date: 2011-05-14
• [Presentation] ヘリコバクターピロリ感染による発癌と炎症の役割 (2011)
  • Author(s): 前田愼
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2011-05-14
• [Presentation] Interleukin-6 (IL-6) plays an important role in epithelial-stromal interactionand promotes gastric tumorigenesis (2011)
  • Author(s): Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R,Nakata W, Sakitani K, Hikiba Y, Akanuma M, Maeda S, Koike K
  • Organizer: DIGESTIVE DISEASE WEEK (DDW)
  • Place of Presentation: Chicago.USA
  • Year and Date: 2011-05-10
• [Presentation] Analysis of the role of JNK and therapeutic effect of JNK inhibition in pancreatic cancer (2011)
  • Author(s): Takahashi R, Nakata W, Kinoshita H, Hayakawa Y, Nakagawa H, Ijichi H, Hirata Y, Maeda S, Koike K
  • Organizer: DIGESTIVE DISEASE WEEK (DDW)
  • Place of Presentation: Chicago. USA.
  • Year and Date: 2011-05-07
• [Presentation] Analysis of the Role of JNK and Therapeutic Effect of JNK Inhibition in Pancreatic Cancer (2011)
  • Author(s): Takahashi R, Nakata W, Kinoshita H, Hayakawa Y, Nakagawa H, Ijichi H, Hirata Y, Maeda S, Koike K
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: アメリカ:Chicago
  • Year and Date: 2011-05-07
• [Presentation] 炎症と胃発癌 (2011)
  • Author(s): 前田愼
  • Organizer: 第100回日本病理学会総会 シンポジウム 3 (感染・炎症と胃癌)
  • Place of Presentation: パシフィコ横浜(神奈川県).
  • Year and Date: 2011-04-29
• [Presentation] 炎症と胃発癌 (2011)
  • Author(s): 前田愼
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-04-29
• [Presentation] Apoptosis signal-regulating kinase 1(ASK1)は JNK-Bim 経路を介したアポトーシスを誘導し肝発癌を抑制する (2010)
  • Author(s): 中川勇人,平田喜裕,早河翼,木下裕人,坂本啓,引場陽子,高橋良太,中田和智子,崎谷康介,小池和彦,小俣政男,前田愼
  • Organizer: 国際科学振興財団フォーラム第18回浜名湖シンポジウム
  • Place of Presentation: アクトシティ浜松コングレスセンター (静岡県)
  • Year and Date: 2010-12-25
• [Presentation] 胃癌に対するプロテアソーム阻害薬(bortezomib)の効果に関する検討. (2010)
  • Author(s): 中田和智子,早河翼,中川勇人,平田喜裕,小池和彦,前田愼
  • Organizer: 第18回日本消化器関連学会週間(JDDW 2010)
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-10-13
• [Presentation] 肝発がんにおける IKK/NF-KBシグナル伝達経路の働き (2010)
  • Author(s): 前田愼
  • Organizer: 第69回日本癌学会学術総会がん征圧へ向けての知の統合(MV2 JCA ・モヴェルネ賞)
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-24
• [Presentation] 膵がん発生における IKKbeta の役割の検討 (2010)
  • Author(s): 前田愼,坂本啓,中川勇人,早河翼,平田喜裕
  • Organizer: 第69回日本癌学会学術総会がん征圧へ向けての知の統合(動物発がんモデル(1))
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [Presentation] 胃癌におけるApoptosis Signal-regulating kinase 1(ASK1)の重要性 (2010)
  • Author(s): 早河翼,平田喜裕,一條秀憲,小俣政男,前 田 愼 , 小 池 和 彦
  • Organizer: 第69回日本癌学会学術総会がん征圧へ向けての知の統合(シグナル伝達 1)
  • Place of Presentation: 大阪国際会議場(大阪府).
  • Year and Date: 2010-09-22
• [Presentation] 胃癌に対するプロテアソーム阻害薬(bortezomib) の効果に関する検討 (2010)
  • Author(s): 中田和智子,早河翼,中川勇人,平田喜裕,小池和彦,前田愼
  • Organizer: 第69回日本癌学会学術総会がん征圧へ向けての知の統合(新規分子標的薬(3))
  • Place of Presentation: 大阪国際会議場(大阪府).
  • Year and Date: 2010-09-22
• [Presentation] Requirement for IKKB in a Mouse Model of Pancreatic Ductal Adenocarcinoma (2010)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Okamoto M Nakagawa H, Hirata Y, Hayakawa Y, Nakata W, Ijichi H, Omata M
  • Organizer: Digestive Disease Week
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-05-07
• [Presentation] Apoptosis Signal-Regulating kinase 1(ASK1)Regulates Colitis andColitis-Associated Tumorigenesis via the lnnate lmmune Responses (2010)
  • Author(s): Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y,Yanai A, Akanuma M, Ogura K, Yoshida H, Omata M, Maeda S.
  • Organizer: DIGESTIVE DISEASE WEEK 2010
  • Place of Presentation: New Orleans.USA.
  • Year and Date: 2010-05-04
• [Presentation] Role of NF-kB in Controlling Citrobacter rodentium-Induced Colitis (2010)
  • Author(s): Hirata Y, Hayakawa Y, Nakagawa H, Nakata W, Sakamoto K, Omata M, MaedaS
  • Organizer: DIGESTIVE DISEASE WEEK
  • Place of Presentation: New Orleans.USA
  • Year and Date: 2010-05-04
• [Presentation] The Impact of IkappaB Kinase Beta in Gastric Carcinogenesis (2010)
  • Author(s): Sakamoto K, Hikiba Y, Nakagawa H, Hayakawa Y, Yanai A, Hirata Y, OguraK, Akanuma M, Maeda S
  • Organizer: DIGESTIVE DISEASE WEEK 2010
  • Place of Presentation: New Orleans. USA.
  • Year and Date: 2010-05-04
• [Presentation] Requirement for IKKB in a Mouse Modelof Pancreatic Ductal Adenocarcinoma (2010)
  • Author(s): Maeda S, Hikiba Y, Sakamoto K, Okamoto M Nakagawa H, Hirata Y, Hayakawa Y, Nakata W, Ijichi H, Omata M
  • Organizer: DIGESTIVE DISEASE WEEK 2010
  • Place of Presentation: New Orleans. USA
  • Year and Date: 2010-05-03