The mechanisms of acquiring chemo-resistance and identification of therapeutic targets in colorectal cancer stem cells.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16571
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: IZUMI Daisuke 熊本大学, 医学部附属病院, 非常勤診療医師 (60594877)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 大腸癌幹細胞 / 抗癌剤耐性

Outline of Final Research Achievements

The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, c-Myc expression was substantially decreased in colorectal CSCs. The c-Myc expression alterations were mediated by upregulation of F-box/WD repeat-containing protein 7 (FBXW7). Differentiated CSCs treated with anticancer agents did not show upregulation of FBXW7 and were more sensitive to irinotecan (CPT-11), highlighting the potential CSC-specific nature of our data. The FBXW7 over-expression was further validated in resected liver metastatic sites in CRC patients after chemotherapy. In conclusion, our study revealed that a CSC-specific FBXW7-regulatory mechanism is strongly associated with resistance to chemotherapeutic agents.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

今回の研究で大腸癌幹細胞特異的なFBXW7調整メカニズムは抗癌剤耐性に強くかかわっていることが分かった。このメカニズムをターゲットとすることで大腸癌幹細胞の新たな治療戦略に寄与することができる可能性がある。