Dissection of the roles of Polycomb complexes for tumor heterogeneity including Cancer Stem Cell in response to microenvironmental shift

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15533
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Harachi Mio 国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (60905553)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: エピゲノム / Polycomb / 悪性脳腫瘍 / 幹細胞 / 治療抵抗性

Outline of Final Research Achievements

We conducted a mechanistic exploration in a cultured system, focusing on the EGFR-Polycomb group signaling in relation to cancer stem cells, which are considered a primary factor in the cure of glioblastoma, the most malignant type of brain tumor.

A bulk transcriptome analysis was performed before and after the induction of cancer stem cells (Neurospheres). The results revealed dynamic changes in the expression of growth signals such as EGFR, various chromatin-binding proteins including the Polycomb group, and chromatin modifications involving DNA. These findings suggest that reverting the epigenomic state could be a potential therapeutic target for cancer cells that have acquired treatment resistance.

Free Research Field

エピゲノム

Academic Significance and Societal Importance of the Research Achievements

本研究は、がん細胞が治療抵抗を示す際に何が起こっているのかという問いについて、発生学の観点を腫瘍分野に持ちこみ、Polycomb群によってがん細胞が初期化を起こし、結果として治療抵抗を示す可能性を示唆する結果を得た。これはがん細胞の治療抵抗性の本質に迫る研究であり、治療標的候補としての可能性を広げる社会的な貢献性だけでなく、正常幹細胞で使われているPolycomb群の機能が、腫瘍になると治療抵抗を獲得する結果となるという、学術的な新規性をもつ。