Identification of genes regulating metastasis in cancer stroma of colorectal cancer.

• Project/Area Number: 16K10558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Sasaki Foundation
• Principal Investigator: Sekiya Takao 公益財団法人佐々木研究所, 附属研究所, 研究所所長(移行) (70142651)
• Co-Investigator(Kenkyū-buntansha): 中村 幸男 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00549488) ; 藤井 智明 公益財団法人佐々木研究所, 附属研究所, 部長(移行) (10511420)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ヒト大腸がん / がん転移 / 間質細胞 / ゼブラフィッシュ / 転移抑制促進遺伝子 / ヒト大腸癌細胞 / 転移促進因子 / 転移促進抑制因子 / ヒト大腸癌 / ゼブラフィシュ

Outline of Final Research Achievements

It has been reported that the interaction between stromal cells and cancer cells plays an important role for metastasis in colorectal cancer. However,their　molecular mechanisms are largely unknown. In this study, the purpose is to clarify the role of stromal cells in colorectal cancer metastasis. We tried to establish a colorectal cancer metastasis model using zebrafish and an insertion mutation transduction system using transposon, and to identify and perform functional analysis of the genes for colorectal cancer metastasis promoting or suppressing in stromal cells. However, we have not identified the genes yet.

Academic Significance and Societal Importance of the Research Achievements

大腸がん患者の死因の多くは、遠隔転移に起因する割合が最も高く、大腸がんの死因の約1/3を占めるが、現段階では、遠隔転移の早期診断法や有効な治療法もない。その理由の一つは、大腸がん転移メカニズムが解明されていないためである。つまり、転移メカニズムの解明は、転移の早期診断法や有効な治療法を開発するための有益な情報となる。

Research Products

• [Journal Article] A novel diagnostic system to evaluate epidermal growth factor receptor impact as a prognostic and therapeutic indicator for lung adenocarcinoma (2020)
  • Author(s): Takakuwa Kazuya、Mogushi Kaoru、Han Min、Fujii Tomoaki、Hosoya Masaki、Yamanami Arina、Akita Tomomi、Yamashita Chikamasa、Hayashida Tetsu、Kato Shunsuke、Yamaguchi Shigeo
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 6214-6214
  • DOI: 10.1038/s41598-020-63200-7
  • Peer Reviewed / Open Access
• [Journal Article] Identification and characterization of a novel <i>adenomatous polyposis coli</i> mutation in adult pancreatoblastoma (2018)
  • Author(s): Yamaguchi S, Fujii T, Izumi Y, Fukumura Y, Han M, Yamaguchi H, Akita T, Yamashita C, Kato S, Sekiya T.
  • Journal Title: Oncotarget Volume: 9(12) Issue: 12 Pages: 10818-10827
  • DOI: 10.18632/oncotarget.24017
  • Peer Reviewed / Open Access
• [Journal Article] Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation. (2018)
  • Author(s): Ikenoue T, Terakado Y, Zhu C, Liu X, Ohsugi T, Matsubara D, Fujii T, Kakuta S,Kubo S, Shibata T, Yamaguchi K, Iwakura Y, Furukawa Y.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 2021-2021
  • DOI: 10.1038/s41598-018-19769-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion. (2016)
  • Author(s): Ikenoue T, Terakado Y, Nakagawa H, Hikiba Y, Fujii T, Matsubara D, Noguchi R, Zhu C, Yamamoto K, Kudo Y, Asaoka Y, Yamaguchi K, Ijichi H, Tateishi K, Fukushima N, Maeda S, Koike K, Furukawa Y
  • Journal Title: Sci Rep Volume: 印刷中 Issue: 1 Pages: 23899-23899
  • DOI: 10.1038/srep23899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An impact of Chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis. (2016)
  • Author(s): Kawai M, Komiyama H, Hosoya M, Okubo H, Fujii T, Yokoyama N, Sato C, Ueyama T, Okuzawa A, Goto M, Kojima Y, Takahashi M, Sugimoto K, Ishiyama S, Munakata S, Ogura D, Niwa S, Tomiki Y, Ochiai T, Sakamoto K:
  • Journal Title: Oncology Letters Volume: 12(6) Issue: 6 Pages: 4773-4778
  • DOI: 10.3892/ol.2016.5271
  • Peer Reviewed / Open Access
• [Presentation] 癌で高頻度に見られる新規FBXW7癌特異的変異条件的ノックインマウスの樹立と解析 (2018)
  • Author(s): 劉 洵,池上 恒雄,寺門 侑美, 朱赤,大杉友之,松原 大祐, 藤井 智明, 角田 茂, 久保 幸子,柴田 琢磨, 山口 貴世志,岩倉洋一郎, 古川 洋一
  • Organizer: 第77回日本癌学会学術集会
• [Presentation] 成人膵芽腫に見られた新規Adenoma polyposis coli (APC)遺伝子変異の機能解析 (2017)
  • Author(s): 泉 祐毅 山口 茂夫 藤井 智明 韓 敏 野崎 由美 山下 親正 加藤 俊介
  • Organizer: 第 15 回日本臨床腫瘍学会学術集会
• [Presentation] Expression and functional analysis of Smyd5 in zebrafish (2016)
  • Author(s): Tomoaki Fujii, Shin-ichiro Tsunesumi, Hiroshi Sagara, Miyo Munakata, Yoshihiro Hisaki, Takao Sekiya,Yoichi Furukawa, Kazuhiro Sakamoto, and Sumiko Watanab
  • Organizer: American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, California, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] 癌で高頻度に見られるFBXW7変異の条件的ノックインマウスの樹立 (2016)
  • Author(s): 池上 恒雄、寺門 侑美、藤井 智明、松原 大祐、山口 貴世志、 古川 洋一
  • Organizer: 第76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: 2016-10-06