Search for therapeutic target factors for small cell lung cancer, focusing on similarity to hematologic tumors and transcriptional regulation of NOTCH family

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16296
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tohoku University
• Principal Investigator: Nishizawa Hironari 東北大学, 医学系研究科, 学術研究員 (30846655)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: フェロトーシス / BACH2 / NOTCH遺伝子 / 悪性リンパ腫 / 小細胞肺癌 / BACH1 / 細胞死伝播 / 線維芽細胞

Outline of Final Research Achievements

The major purpose of this study was to discover novel target factors for small cell lung cancer in terms of the overlap between prognostic factors for malignant lymphoma and transcription factors that regulate the transcription of the NOTCH genes, but we were unable to unearth as many promising therapeutic targets as initially expected. However, we did obtain data suggesting that BACH2, a prognostic factor in malignant lymphoma, may repress NOTCH gene transcription in human-derived lung cancer cell lines, albeit to a limited extent. This point will be pursued further in the future.
In parallel, we also searched for regulators of iron-dependent cell death ferroptosis and found that BACH2 promotes ferroptosis and that ferroptosis is transmitted from cell to cell and ferroptosis occurs by BACH1-re-expression, which we published in papers.

Free Research Field

細胞死、フェロトーシス、細胞老化、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

フェロトーシスは生体内でがん抑制機構として働くことが分かっており、血液腫瘍や小細胞肺癌を含め、悪性腫瘍への新規治療手段として注目されている。本研究によって、悪性リンパ腫の予後因子であるBACH2がフェロトーシスを制御することが示唆されたのは、フェロトーシス研究において重要な発見だと考えられる。加えて、フェロトーシスの細胞間伝播現象とBACH2のFamily因子であるBACH1の再発現によるフェロトーシスモデル機構を発見したことで、将来的に、腫瘍内で線維芽細胞や免疫細胞でBACH1を再発現させてフェロトーシスを引き起こし腫瘍内へ伝播させるという細胞療法の開発に繋げられる可能性がある。