Elucidation of new alimentally cancer disease mechanism of Cullin3 E3 ligase mediated by BTB protein

• Project/Area Number: 15K19343
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Ozeki Keiji 名古屋市立大学, 大学院医学研究科, 助教 (70750610)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 大腸癌 / BTB蛋白 / Cullin3 / ユビキチン / 異所性胃型粘液形質 / BTB蛋白質 / KLHL / LST / 異所性胃型形質 / 消化器癌 / BTB-ZnF ドメイン蛋白 / 胃癌 / ユビキチン化 / BTB-ZnFドメイン蛋白 / Ｃｕｌｌｉｎ３

Outline of Final Research Achievements

BTB protein - Cullin 3 - E 3 ligase has been reported that they may become a new therapeutic target in cancer cells, although there are many unclear points about the function of about BTB proteins. BTB protein (BACK-Kelch protein group) strongly binding to Cullin 3 was identified by using Alpha screening assay. We found a BTB protein (KLHL-X) associated with cell proliferation, due to comprehensively performing SiRNA of BTB protein on colon cancer cell line. Further examinations showed that the expression of KLHL-X might be involved in proliferation and invasion in colorectal cancer.
Next, the relationship of ectopic gastric mucinous phenotype and colorectal lateral spreading tumors (LSTs) are not reported. We analyzed 105 colorectal LSTs to identify factors indicative of malignant transformation and invasion. Ectopic gastric and intestinal phenotype, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade on colorectal LSTs.

Research Products

• [Journal Article] Expression and subcellular localization of AT motif binding factor 1 in colon tumours. (2017)
  • Author(s): Kataoka H, Miura Y, Kawaguchi M, Suzuki S, Okamoto Y, Ozeki K, Shimura T, Mizoshita T, Kubota E, Tanida S, Takahashi S, Asai K, Joh T.
  • Journal Title: Mol Med Rep Volume: 16 Issue: 3 Pages: 3095-3102
  • DOI: 10.3892/mmr.2017.7016
  • Peer Reviewed
• [Journal Article] Ectopic Gastric and Intestinal Phenotypes, Neuroendocrine Cell Differentiation, and SOX2 Expression Correlated With Early Tumor Progression in Colorectal Laterally Spreading Tumors. (2016)
  • Author(s): Katano T, Mizoshita T, Tsukamoto H, Nishie H, Inagaki Y, Hayashi N, Nomura S, Ozeki K, Okamoto Y, Shimura T, Mori Y, Kubota E, Tanida S, Kataoka H, Kuno T, Takahashi S, Joh T.
  • Journal Title: Clin Colorectal Cancer. Volume: - Issue: 2 Pages: 141-146
  • DOI: 10.1016/j.clcc.2016.09.009
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 大腸癌の進展と関連した新規因子の機能解析 (2017)
  • Author(s): 西江 裕忠, 尾関 啓司、久保田 英嗣, 片岡 洋望,城 卓志
  • Organizer: 第36回消化器病態生理勉強会
• [Presentation] 大腸癌の進展と関連した新規因子の機能解析 (2017)
  • Author(s): 西江 裕忠, 尾関 啓司、片岡 洋望、城 卓志
  • Organizer: 第14回日本消化管学会学術集会
• [Presentation] 大腸側方発育型腫瘍における悪性化・粘膜下層浸潤予測因子の臨床病理学的検討 (2017)
  • Author(s): 片野 敬仁、尾関 啓司、片岡 洋望、城 卓志
  • Organizer: 第59回日本消化器病学会学術集会