Analysis of HIF-1a mediated cancer stem cell maintenance in lung cancer cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17233
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: National Center for Global Health and Medicine (2021-2022); Nippon Medical School (2020)
• Principal Investigator: Iwabuchi chisato 国立研究開発法人国立国際医療研究センター, 研究所, 疾患ゲノム研究部 研究員 (20514441)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺がん / HIF-1a / 癌幹細胞

Outline of Final Research Achievements

In this research project, we focused on the maintenance mechanism of cancer stem cells in lung cancer, which is one of the most common causes of cancer death in Japan. It has been reported that cancer stem cells are deeply involved in the acquisition of drug resistance and metastasis, and the applicant has previously shown that lung cancer cells acquire drug resistance and the number of cancer stem cells increases when the expression of HIF-1a, a hypoxia response factor, is upregulated. In this study, we focused on the O-Glc-Nac modification, a protein modification that is known to regulate protein function in the same way as the O-Glc-Nac oxidative modification, and is a type of glycolytic modification. It is a type of glycolytic system.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

肺がんは男女ともに死亡率上位となる予後不良な疾患の１つである。効果的な治療法の開発は重要で急務である。本研究課題で着目した癌幹細胞は癌の転移や薬剤耐性獲得に大きく影響を及ぼす細胞である。この細胞の維持機構を破綻させることができれば薬剤耐性獲得解除や転移を防げる可能性を秘めており研究成果は多くの肺がん患者のQOLを向上させるのに有益な基礎研究の結果になると予想される。さらに他の癌においても応用が可能かもしれない。申請者が報告してきたEGFR陽性NSCLC細胞でのHIF-1αによる薬剤耐性獲得機構に関する研究はこれまで報告がなく独自の研究である。