Establishment of a novel anti-cancer strategy model utilizing extracellular lipid addiction of tumor cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yamamoto Kouhei 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (50451927)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん / 細胞死 / フェロトーシス / 新規治療戦略

Outline of Final Research Achievements

Regarding the mechanism of the decrease in protein levels of GPX4 due to a decrease in extracellular fatty acids, cellular experiments confirmed that FABP5 controls the expression level of GPX4 at the protein level. This phenomenon was not due to the amount of extracellular fatty acids, but rather to the concentration of extracellular selenium, which has a significant effect on intracellular GPX4. This was also the case for GPX1, a member of the same glutathione peroxidase group. On the other hand, the selenoprotein TXNRD1 was not significantly affected by extracellular selenium levels, an interesting finding.

Free Research Field

腫瘍病理学

Academic Significance and Societal Importance of the Research Achievements

セレン元素を必須とするセレノプロテインのなかでもグルタチオンペルオキシダーゼ群での細胞外セレン元素量に対する影響が強く、TXNRD群ではその影響がほとんど認めないことから、セレノシステイン残基を用いたセレン元素の取り込みに関し、セレノプロテイン間で大きなメカニズムの違いが存在することが示唆された。