Exploration of transcription factors that induce tumor-promoting subsets of breast carcinoma-associated fibroblasts

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20837
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Juntendo University
• Principal Investigator: Mezawa Yoshihiro 順天堂大学, 医学部, 助教 (50966538)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 癌微小環境 / 癌関連線維芽細胞 / 乳癌 / 転写因子

Outline of Final Research Achievements

In the tumor-microenvironment, carcinoma-associated fibroblasts (CAFs) promote regulating the malignancy and antitumor immunity through promoting desmoplastic reaction and tumor inflammation. This study aimed to identify transcription factors governing the properties of cancer-promoting subpopulations in breast cancer. Transcriptome analysis, epigenome analysis of CAF cell lines, and meta-analysis of public transcriptome data of human breast cancers were conducted. As the results, we reveal various transcription factors that expression and activity were increased in CAF subpopulations. The present study provides fundamental information for developing CAF-targeted therapy.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

CAFは癌細胞の増殖、浸潤・転移、治療抵抗性、血管新生、腫瘍免疫抑制などを通じて癌促進的な機能が多く知られている。一方、癌抑制的な機能も報告されており、CAFの亜集団の特性の理解がCAFの機能制御に基づいた治療の実現には必須と考えられるが、創薬応用には十分な知見が集積していない。本研究では、細胞の性質を規定する最も重要な要素である転写因子に着目し、乳癌CAFの不均一性をmRNAレベルで解析し、亜集団形成に関与することが示唆される転写因子を複数見出した。これらの知見はCAF亜集団を制御し、治療効果を増加させる手法の開発に向けて重要な意義を持つ。