A novel invasion-related gene involved in tumor recurrence after radiation therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22595
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Harada Hiroshi 京都大学, 生命科学研究科, 教授 (80362531)
• Co-Investigator(Kenkyū-buntansha): 森鳰 章代 京都大学, 生命科学研究科, 研究員 (20722648) ; 小林 稔 京都大学, 生命科学研究科, 特定助教 (40644894)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: がん / 低酸素 / 浸潤・転移関連遺伝子 / 放射線治療 / 放射線抵抗性 / HIF-1

Outline of Final Research Achievements

We previously demonstrated in cell lineage experiments of hypoxic cancer cells that cancer cells responsible for tumor recurrence after radiation therapy are predominantly present in hypoxic regions within a tumor tissue. It was also clarified that during the recurrence process, hypoxic cancer cells that survive radiation therapy infiltrate toward the tumor blood vessels, causing cancer recurrence. However, the gene that induces the infiltration ability of hypoxic cancer cells has not been identified yet. In this study, we developed a screening experiment to search for the gene and could successfully identify a novel gene. We found that the expression of the gene was induced at the transcription initiation level in a hypoxia-inducible transcription factor (HIF-1)-dependent manner. An in vitro scratch assay also confirmed its ability to induce invasiveness of cancer cells under hypoxia.

Free Research Field

がん細胞生物学、低酸素バイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究によって、低酸素がん細胞の浸潤能を担う新たな責任遺伝子を同定することが出来、かつその発現制御機構の一端が明らかになった。今後、更に発現制御機構の詳細を明らかにすることで、当該新規遺伝子の機能を阻害し、がんの浸潤能を抑制、そして放射線治療後の再発を抑える新たな治療法の確立に繋がることが期待される。