The analysis of gene expression changes in the early stages of breast cancer metastasis using a zebrafish xenograft model.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Chiba University
• Principal Investigator: Mizoguchi Takamasa 千葉大学, 大学院薬学研究院, 助教 (10645419)
• Co-Investigator(Kenkyū-buntansha): 高橋 広夫 金沢大学, 薬学系, 准教授 (30454367)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: MIB1 / CTNND1 / 乳がん / 細胞移動 / E-cadherin

Outline of Final Research Achievements

Database-based analysis and biochemical and cell biological analysis using various breast cancer-derived cell lines revealed that breast cancer cell migration is enhanced by decreased E3 ubiquitin ligase Mindbomb1 (MIB1) expression. In breast cancer cells, MIB1 stabilizes cell-cell adhesion and inhibits cell migration by regulating the protein level of Catenin delta1 (CTNND1), an E-cadherin interacting protein.
Our results suggest the possibility that breast cancer metastasis can be predicted by measuring the expression level of MIB1 and the protein level of CTNND1 in breast cancer cells in patients. In addition, our results also suggest that breast cancer metastasis may be inhibited by enhancing the function of MIB1. Therefore, our results may lead to new breast cancer therapies, such as treatment of the primary tumor while inhibiting metastasis by combining existing breast cancer treatment strategies.

Free Research Field

病態モデル、発生生物学、分子細胞生物学、生化学

Academic Significance and Societal Importance of the Research Achievements

乳がん患者のがん細胞におけるMIB1の発現レベル、CTNND1のタンパク質量レベルを計測することにより乳がんの転移しやすさが予測できることが示唆された。また本研究成果からMIB1の機能を亢進することで乳がんの転移を抑制できる可能性も考えられる。よって本研究成果は既存の乳がん治療戦略と併用することで、転移を抑制しつつ原発巣の根治治療を進めるといった、新たな乳がん治療の創出にもつながると考えられる。