Study of the Phosphate Exporter XPR1 function in Ovarian Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hayashi Tomoatsu 東京大学, 定量生命科学研究所, 特任助教 (30583215)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: XPR1 / Phosphate transporter / 卵巣がん / 卵巣明細胞がん / Apoptosis

Outline of Final Research Achievements

In this study, we reported in a paper (Akasu-Nagayoshi et al., Cancer Sci, 2022) that suppression of XPR1 expression in ovarian clear cell carcinoma (OCCC) cells significantly inhibits their proliferation. Furthermore, we found that OCCC cells with constitutively suppressed XPR1 expression exhibit a marked reduction in tumorigenicity when transplanted into immunodeficient mice. In addition, we investigated the molecular mechanism of cell death induction by XPR1 inhibition and revealed that inhibiting XPR1 increases intracellular phosphorus levels, enhances oxidative stress, and activates the NFkB signaling pathway.　Moreover, we conducted a metabolomic analysis upon suppression of XPR1 expression in OCCC cells and found a significant increase in the metabolites of specific signaling pathways important for oxidative stress response.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

卵巣がんは、欧米においては80%近くが漿液性卵巣がんなのに対して、日本を含む東アジア圏では卵巣明細胞がんが約30%と高い割合を占める。また、卵巣明細胞がんは、腫瘍内の不均一性が高く化学療法に対しても抵抗性を有する。私たちはリンの排出を制御するXPR1が卵巣明細胞がんに対して有用な治療標的分子であることを報告した。また、XPR1は卵巣がんをはじめ様々ながんで発現が亢進しており、卵巣がんのみならず様々ながんにおける有望な治療標的分子となる可能性がある。引き続き、XPR1の機能解析および創薬研究を進めることで、卵巣明細胞がんの発がん機構の分子基盤の解明および画期的な新薬の創製が期待される。