SOX17 suppression and inflammation in malignant cancer progression

• Project/Area Number: 25430107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Oshima Hiroko 金沢大学, がん進展制御研究所, 准教授 (80362515)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: SOX17 / マウスモデル / 大腸がん / 消化器がん / 炎症 / 粘膜下浸潤

Outline of Final Research Achievements

Transcription factor SOX17 has been shown to function as “tumor promoter” and also “tumor suppressor”, and the role of SOX17 in tumorigenesis has not yet been elucidated. In this project, the roles of SOX17 in intestinal tumor development and malignant progression with submucosal invasion have been examined by mouse genetic studies. We found that SOX17 expression is induced by Wnt signaling-dependent manner in tumor cells. However, disruption of SOX17 gene did not cause any morphological change of intestinal tumors. Moreover, the number, size, and invasion status of intestinal tumors were not changed by SOX17 disruption. These results indicate that SOX17 is dispensable for intestinal tumor development and malignant progression.

Research Products

• [Journal Article] Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment. (2016)
  • Author(s): Maeda Y, Echizen K, Oshima H, Yu L, Sakulsak N, Hirose O, Yamada Y, Taniguchi T, Jenkins BJ, Saya H, Oshima M.
  • Journal Title: Cancer prevention research Volume: 9 Issue: 3 Pages: 253-263
  • DOI: 10.1158/1940-6207.capr-15-0315
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. (2016)
  • Author(s): Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 2 Pages: 140-148
  • DOI: 10.1111/cas.12849
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dipeptide species regulate nutrient signalling essential for the maintenance of chronic myelogenous leukaemia stem cells. (2015)
  • Author(s): Naka K, Jomen Y, Ishihara K, Kim J, Ishimoto T, Bae E, Mohney R, Stirdivant SM, Oshima H, Oshima M, Kim DW, Nakauchi H, Takihara Y, Kato Y, Ooshima A, Kim SJ.
  • Journal Title: Nature Communication Volume: 6 Issue: 1 Pages: 8039-8039
  • DOI: 10.1038/ncomms9039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Suppressing TGFβ signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause invasive intestinal cancer. (2015)
  • Author(s): Oshima H, Nakayama M, Han TS, Naoi K, Ju X, Maeda Y, Robine S, Tsuchiya K, Sato T, Sato H, Taketo MM, Oshima M.
  • Journal Title: Cancer Res. Volume: 75 Issue: 4 Pages: 766-776
  • DOI: 10.1158/0008-5472.can-14-2036
  • NAID: 120005593962
  • Peer Reviewed / Open Access
• [Journal Article] Ink4a/Arf-dependent Loss of Parietal Cells Induced by Oxidative Stress Proomtes CD44-dependent Gastric Tumorigenesis (2015)
  • Author(s): Seishima R, Wada T and Tsuchihashi K, Okazaki S, Yoshikawa M, Oshima H., Oshima M., Sato T., Hasegawa H., Kitagawa Y., Goldenring JR., Saya H., Nagano O.
  • Journal Title: Cancer Prevention Research Volume: in press
  • Peer Reviewed
• [Journal Article] MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. (2015)
  • Author(s): Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, Chang AN, Goel A, Yang HK.
  • Journal Title: Gut Volume: 64 Issue: 2 Pages: 203-214
  • DOI: 10.1136/gutjnl-2013-306640
  • Peer Reviewed
• [Journal Article] TNF-a/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells (2014)
  • Author(s): Oshima H, Ishikawa T, Yoshida GJ, et al.
  • Journal Title: Oncogene Volume: 33 Issue: 29 Pages: 3820-3829
  • DOI: 10.1038/onc.2013.356
  • Peer Reviewed / Open Access
• [Journal Article] The role of PGE2-associated inflammatory responses in gastric cancer development (2013)
  • Author(s): Oshima H, and Oshima M
  • Journal Title: Semin Immunopathol Volume: 47 Issue: 2 Pages: 139-150
  • DOI: 10.1007/s00281-012-0353-5
  • Peer Reviewed
• [Presentation] Cooperation of TGF-β suppression and inflammation in malignant progression invasion of intestinal tumors. (2015)
  • Author(s): Oshima H, Nakayama M, Sato H, Taketo MM, Oshima M.
  • Organizer: 第７４回 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] TGF-βシグナル抑制による大腸がん浸潤 (2015)
  • Author(s): 大島浩子、中山瑞穂、佐藤博、大島正伸
  • Organizer: 平成２６年度「がん研究分野の特性等を踏まえた支援活動」公開シンポジウム
  • Place of Presentation: 一橋講堂(学術総合センター2F)
  • Year and Date: 2015-01-27 – 2015-01-28
• [Presentation] Chronic inflammation and TGFβ signaing suppression in invasive gastrointestinal cancer development (2014)
  • Author(s): Oshima H, Nakayama M, Sato H, Taketo MM, Oshima M
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] TGF-βシグナル抑制と慢性炎症反応による大腸がん浸潤機構 (2014)
  • Author(s): 大島浩子，中山瑞穂，大島正伸
  • Organizer: 平成25年度文部科学省新学術領域「がん支援」公開シンポジウム
  • Place of Presentation: 東京・学術総合センター
• [Presentation] The role of inflammation in development of invasive intestinal adenocarcinoma (2013)
  • Author(s): Oshima H, Nakayama M, Taketo M, Oshima M.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜・パシフィコ横浜
• [Presentation] TNF-a signaling in bone marrow-derived cells promotes gastric tumorigenesis through Noxo1 expression (2013)
  • Author(s): Oshima H, Naka K, Oshima M
  • Organizer: 4th JCA-AACR Special Joint Conference: The Latest Advances in Gastric Cancer Research
  • Place of Presentation: 千葉・東京ベイ舞浜ホテル
• [Remarks] 金沢大学がん進展制御研究所 腫瘍遺伝学研究分野
  • URL: http://genetics.w3.kanazawa-u.ac.jp
• [Remarks] 金沢大学がん進展制御研究所 腫瘍遺伝学研究分野
  • URL: http://genetics.w3.kanazawa-u.ac.jp