Elucidation of the potential role of the cystine/glutamate transporter in the regulation of tumor metastasis through interaction with integrin

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15481
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Niigata University
• Principal Investigator: Sato Mami 新潟大学, 日本酒学センター, 特任助教 (40893235)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: xCT / シスチン / フェロトーシス

Outline of Final Research Achievements

Deletion or overexpression of the xCT gene attenuated adhesion capacity to endothelial cells and tumor cell growth (3D culture model) in HT1080, a human fibrosarcoma-derived cell line. Downregulation of N-Cadherin might be one of the mechanisms behind these phenomena. xCT is also one of the ferroptosis regulators, and sorafenib, a molecular target drug, has been used as an inhibitor of xCT for ferroptosis-cancer-relevant research. Thus, the xCT inhibition manner of sorafenib was characterized to investigate if xCT inhibition can regulate cancer metastasis through ferroptosis induction. As a result, the induction of cell death by sorafenib was independent of xCT expression. Additionally, it has been confirmed that sorafenib does not induce ferroptosis in many cancer cell lines.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

研究者らはこれまでにマウスメラノーマ細胞におけるxCT遺伝子欠損（xCT-KO）が転移能の低下と関連することを示したが、本研究でヒト由来がん細胞においても同様の結果を得た。そのメカニズムとして、細胞間接着の低下によることを示唆した。この成果は、xCTの役割として注目されてきた酸化ストレスからの細胞の保護に加え、新たにxCTと接着因子との関連性を示した点で意義がある。