Therapeutic strategies based on the zinc transporter-mediated molecular pathology of colorectal cancer.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08354
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Shizuoka (2023); Keio University (2020-2022)
• Principal Investigator: Ohashi Wakana 静岡県立大学, 薬学部, 准教授 (50381596)
• Co-Investigator(Kenkyū-buntansha): 早川 芳弘 富山大学, 学術研究部薬学・和漢系, 教授 (10541956) ; 井村 穣二 獨協医科大学, 医学部, 非常勤講師 (80316554)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 亜鉛 / 大腸がん / 微量元素 / 腸上皮細胞

Outline of Final Research Achievements

The study focused on the role of ZIP7, which is essential to maintain the intestinal stem cells and cell growth of transit-amplifying cells in the small intestine in mice, in the pathogenesis of colorectal cancer. The role of ZIP7 expression in tumorigenesis in vivo was investigated by subcutaneously implanting ZIP7-overexpressing cancer cells into the flanks of nude mice. We found that increased expression of ZIP7 enhanced the tumor formation. We investigated the effect of ZIP7 expression on cancer cell properties including cell growth and migration and found that overexpression of ZIP7 affected cellular functions, suggesting that ZIP7 can contribute to malignant progression. In addition, we found that increased expression of ZIP7 induced changes in cancer cell metabolism and analyzed the metabolites that were altered by ZIP7 expression.

Free Research Field

金属生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により大腸がん悪性化における亜鉛トランスポーターZIP7の寄与が示唆された。また、この寄与に関わる分子機構の一端が示された。本研究は、大腸がん悪性化進展の分子病態機構の解明に新しい展開を与えるとともに、現時点で確立された治療法のない悪性化進展抑制を目指した療法の開発を模索していく上で意義のある研究となったと思われる。