Functional analysis of colorectal cancer stem cells by cellular physiological approach focused on cellular volume regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16456
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kudou Michihiro 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (20804264)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 大腸癌 / 癌幹細胞 / イオン輸送体 / アポトーシス

Outline of Final Research Achievements

CLCN5, LRRA8a, and AQP5, which are ion transporters related to the regulation of cell volume under hypotonicity, overexpressed in colon cancer stem cells (CSCs）, suggesting that CSCs have the resistance to hypotonic shock. The measurement of cell volume in the CSCs and normal cancer cells (NSCs) under hypotonicity revealed that NSCs could not survival under severe hypotonicity; on the other hands, CSCs could survive and avoid cell rupture. LRRC8a gene knockdown or AQP inhibition using drugs suppressed the resistance of hypotonicity. The results showed that LRRC8a or AQP1 are associated with specific cell volume regulation in CSCs. The molecules may be the candidate genes for developing the targeted therapies to CSCs.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

癌幹細胞標的治療は開発が望まれており、再発や治療抵抗性を打破する強力な治療となる可能性がある。今回発見された細胞容積調整に関与する癌幹細胞に高発現する分子(LRRC8a, AQP1, CLCN5)は、癌のアポトーシスにも関与していることが広く報告されている。それゆえに、これら分子を標的とした薬剤や、低浸透圧刺激を利用した治療を開発することができれば、癌治療の発展に大きく寄与する可能性がある。