Roles of novel target genes of Cdx1/2 in differentiation and transformation of intestinal epithelial cells.

• Project/Area Number: 20390110
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto University
• Principal Investigator: AOKI Masahiro Kyoto University, 分子病態学部, 部長 (60362464)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 大腸癌 / 転写因子 / 短鎖脂肪酸 / GEF / CDX2 / PLEKHG1 / ノックアウトマウス / 14-3-3 / SLC5A8 / 酪酸 / CDX1

Research Abstract

Expression of the Slc5a8 gene encoding a short-chain fatty acid transporter was positively regulated by Cdx1/2 in vivo, and its level was reduced in the colonic polyps of Apc mutant mice, accompanied by decreased expression of Cdx2. Plekhg1 was shown to be a direct target gene of Cdx1/2. Plekhg1 was involved in E-cadherin-mediated cell-cell adhesion, and bound to 14-3-3 only when phosphorylated at serine 611.

Research Products

• [Journal Article] Inactivation of chemokine (C-Cmotif) receptor 1 (CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model (2010)
  • Author(s): Kitamura T, Fujishita T, Loetscher P, Revesz L, Hashida H, Kizaka-Kndoh S, Aoki M, Taketo, MM
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 13063-13068
  • Peer Reviewed
• [Journal Article] LKB1 suppresses p21-activated kinase-1 (PAK1) by phosphorylation of Thr109 in the p21-binding domain. (2010)
  • Author(s): Deguchi A, Miyoshi H, Kojima Y.Okawa K, Aoki M, Taketo, M.M.
  • Journal Title: J Biol Chem 285 Pages: 18282-18290
  • Peer Reviewed
• [Journal Article] CDX Transcription Factors Positively Regulate Expression of Solute Carrier Family 5 (2010)
  • Author(s): Kakizaki F, Aoki K, Miyoshi H, Carrasco N, Aoki M, Taketo MM
  • Journal Title: Member 8 in the Colonic Epithelium. Gastroenterology 138 Pages: 627-635
  • Peer Reviewed
• [Journal Article] LKB 1 suppresses p21-activated kinase-1(PAK1) by phosphorylation of Thr109 in the p21-binding domain. (2010)
  • Author(s): Deguchi, A., et al.
  • Journal Title: J Biol Chem. Volume: 285 Pages: 18282-18290
  • Peer Reviewed
• [Journal Article] Inactivation of chemokine(C-C motif) receptor 1(CCR1) suppresses colon cancer liver metastasis by blocking accumulation of immature myeloid cells in a mouse model (2010)
  • Author(s): Kitamura, T., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 13063-13068
  • Peer Reviewed
• [Journal Article] Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling. (2010)
  • Author(s): Sonoshita, M., et al.
  • Journal Title: Cancer Cell Volume: 19 Pages: 125-137
  • Peer Reviewed
• [Journal Article] Suppression of colonic polyposis by homeoprotein CDX2 through its non-transcriptional function that stabilizes p27Kip1. (2010)
  • Author(s): Aoki, K., et al.
  • Journal Title: Cancer Res. Volume: 71 Pages: 593-602
  • Peer Reviewed
• [Journal Article] CDX Transcription Factors Positively Regulate Expression of Solute Carrier Family 5, Member 8 in the Colonic Epithelium (2010)
  • Author(s): Kakizaki, F., et al.
  • Journal Title: Gastroenterology 138 Pages: 627-635
  • Peer Reviewed
• [Journal Article] Reduced Level of Smoothened Suppresses Intestinal Tumorigenesis by Down-Regulation of Wnt Signaling. (2009)
  • Author(s): Arimura S, Matsunaga A, Kitamura T, Aoki K, Aoki M, Taketo MM
  • Journal Title: Gastroenterology 137 Pages: 629-638
  • Peer Reviewed
• [Journal Article] Hepatocellular carcinoma development induced by conditional beta-catenin activation in Lkb1 mice (2009)
  • Author(s): Miyoshi H, Deguchi A, Nakau M, Kojima Y, Mori A, Oshima M, Aoki M, Taketo MM
  • Journal Title: Cancer Sci 100 Pages: 2046-2053
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas. (2009)
  • Author(s): Kitamura T, Biyajima K, Aoki M, Oshima M, Taketo MM
  • Journal Title: Lab Invest 89 Pages: 98-105
  • Peer Reviewed
• [Journal Article] Reduced Level of Smoothened Suppresses Intestinal Tumorigenesis by Down-Regulation of Wnt Signaling (2009)
  • Author(s): Arimura, S., et al.
  • Journal Title: Gastroenterology 137 Pages: 629-638
  • Peer Reviewed
• [Journal Article] Hepatocellular carcinoma development induced by conditional beta-caten in activation in Lkb1+/- mice (2009)
  • Author(s): Miyoshi, H., et al.
  • Journal Title: Cancer Sci. 100 Pages: 2046-2053
  • Peer Reviewed
• [Journal Article] The role of mTORC1 pathway in intestinal tumorigenesis (2009)
  • Author(s): Fujishita, T., et al.
  • Journal Title: Cell Cycle 8 Pages: 3684-3687
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas. (2009)
  • Author(s): Kitamura, T., et al.
  • Journal Title: Lab. Invest. 89 Pages: 98-105
  • Peer Reviewed
• [Journal Article] Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice (2008)
  • Author(s): Fujishita T, Aoki K, Lane HA, Aoki M, Taketo MM
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 13544-13559
  • Peer Reviewed
• [Journal Article] Activated macrophages promote Wnt signalling through tumour ecrosis factor-alpha in gastric tumour cells. (2008)
  • Author(s): Oguma K, Oshima H, Aoki M, Uchio R, Naka K, Nakamura S, Hirao A., Saya H, Taketo MM, Oshima M
  • Journal Title: Embo J 27 Pages: 1671-1681
  • Peer Reviewed
• [Journal Article] Inhibition of the mTORC1 pathway suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice. (2008)
  • Author(s): Fujishita, T., et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 13544-13559
  • Peer Reviewed
• [Journal Article] Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. (2008)
  • Author(s): Oguma, K., et al.
  • Journal Title: Embo. J. 27 Pages: 1671-1681
  • Peer Reviewed
• [Presentation] LKB1はPAK1のp21結合ドメイン内のThr109をリン酸化することによりそのキナーゼ活性を抑制する (2011)
  • Author(s): 出口敦子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2011-09-23
• [Presentation] Critical roles of Notch signaling in colon cancer metastasis (2010)
  • Author(s): 園下将大
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-09
• [Presentation] 転写因子CDX は癌抑制遺伝子の候補solute carrier family 5, member 8(SLC5A8)の発現を制御する (2010)
  • Author(s): 柿崎文彦
  • Organizer: 第29回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-09
• [Presentation] JNK signaling promotes intestinal tumorigenesis through mTORC1 pathway activation in ApcΔ716 mice (2010)
  • Author(s): 藤下晃章
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-08
• [Presentation] JNK signaling promotes intestinal tumorigenesis through mTORC1 pathway activation in Apc Δ716 mice. (2010)
  • Author(s): 藤下晃章
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-08
• [Presentation] ヘッジホッグ経路シグナル伝達分子SmoothenedによるWntシグナル伝達経路を介した腸管腫瘍形成の促進 (2010)
  • Author(s): 有村純暢
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2010-10-28
• [Presentation] mTOR経路の活性化はApcマウスの腫瘍形成を促進する (2010)
  • Author(s): 藤下晃章
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2010-10-28
• [Presentation] 消化管腫瘍形成におけるSmoothened及びmTORC1の役割 (2010)
  • Author(s): 青木正博
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2010-10-02
• [Presentation] LKB1 はPAK1のp21結合ドメイン内のThr109をリン酸化することによりそのキナーゼ活性を抑制する (2010)
  • Author(s): 出口敦子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] 転写因子CDXは大腸上皮においてSLC5A8遺伝子の発現を正に制御する (2010)
  • Author(s): 柿崎文彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] JNKシグナルはmTORC1経路活性化を介してApc変異マウスにおける腸管腫瘍形成を促進する (2010)
  • Author(s): 藤下晃章
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-22
• [Presentation] Roles of Smoothened (Smo), the major signal transducer of the hedgehog pathway, in the development of intestinal tumors (2010)
  • Author(s): 青木正博
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting
  • Place of Presentation: San Diego, CA (USA)
  • Year and Date: 2010-04-15
• [Presentation] ヘッジホッグ経路シグナル伝達分子SmoothenedによるWntシグナル伝達経路を介した腸管腫瘍形成の促進 (2010)
  • Author(s): 有村純暢
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都国際会議場(京都)
  • Year and Date: 2010-03-28
• [Presentation] ヘッジホッグ経路シグナル伝達分子SmoothenedによるWntシグナル伝達経路を介した腸管腫瘍形成の促進 (2009)
  • Author(s): 有村純暢
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] 消化管腫瘍形成における Smoothened 及びmTORC1の役割 (2009)
  • Author(s): 青木正博
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜、日本
• [Presentation] 転写因子CDXは癌抑制遺伝子の候補solute carrier family 5, member 8 (SLC5A8)の発現を制御する (2008)
  • Author(s): 柿崎文彦
  • Organizer: 第29回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ヘッジホッグ経路シグナル伝達分子SmoothenedによるWntシグナル伝達経路を介した腸管腫瘍形成の促進 (2008)
  • Author(s): 有村純暢
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] mTOR経路の活性化はApcマウスの腫瘍形成を促進する (2008)
  • Author(s): 藤下晃章
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Roles of Smoothened (Smo), the major signal transducer of the hedgehog pathway, in the development of intestinal tumors (2008)
  • Author(s): Masahiro Aoki
  • Organizer: 2008 American Association for Cancer Research (AACR) Annual Meeting
  • Place of Presentation: San Diego, CA (USA)
  • Year and Date: 2008-04-15
• [Book] マウス・ラット疾患モデル活用ハンドブック (2010)
  • Author(s): 青木正博
  • Publisher: 羊土社
• [Remarks] ホームページ等