Novel gene network responsible for hypoxic response and radioresistance of cancer cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: Morinibu Akiyo 京都大学, 生命科学研究科, 研究員 (20722648)
• Co-Investigator(Kenkyū-buntansha): 小林 稔 京都大学, 生命科学研究科, 特定助教 (40644894) ; 原田 浩 京都大学, 生命科学研究科, 教授 (80362531) ; 子安 翔 京都大学, 医学研究科, 特定病院助教 (80781913)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: がん / 放射線 / 低酸素 / 放射線抵抗性

Outline of Final Research Achievements

It is known that cancer cells acquire radioresistance in hypoxic regions of malignant solid tumors. In order to overcome the problem, here we focused on two genes, which we found to be expressed in hypoxic environment and induce radioresistance, and analyzed their mechanism of action and function. First, we found that the expression of Shh, which is a ligand of the sonic hedgehog pathway, increased under hypoxic environment in a HIF-1-dependent manner. Shh protein was secreted from hypoxic cells, increased hypoxic fraction in tumor tissue by inducing fibroblast proliferation, and eventually enhanced radioresistance of tumor tissue. We also discovered a novel gene that is expressed and secreted in response to hypoxic stimulation, and elucidated molecular mechanism about how it induced radioresistance of hypoxic cells.

Free Research Field

放射線腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究プロジェクトにより、低酸素環境下でがん細胞の放射線抵抗性を惹起する2つの遺伝子経路が同定された。当該遺伝子ネットワークを治療標的とすることで、低酸素がん細胞の放射線抵抗性を抑制し、がんの再発を抑制する新たな治療法の確立に繋がることが期待される。