Analysis of the mechanism of hypoxia stress response in adult t-cell leukemia (ATL)

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: University of Miyazaki
• Principal Investigator: Nakahata Shingo 宮崎大学, 医学部, 講師 (80437938)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 低酸素 / NDRG2 / ATL

Outline of Final Research Achievements

This study suggested that, as a response to hypoxia, the regulation of phosphorylation of cellular signaling molecules by NDRG2 plays an important role in the growth of cancer cells. NDRG2 regulates various signaling pathways including PI3K/AKT and NF-κB. This study also suggested NDRG2 is involved in the function of hematopoietic stem cells (HSCs) and may play a role in the regulation of hypoxia response of HSCs in the bone marrow niche. In addition, the downregulation of p47 expression via the autophagy-lysosome pathway contributes to the activation of NF-κB in ATL.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

癌抑制遺伝子として同定したNDRG2が癌の低酸素適応・抵抗性の機構解明の鍵となる分子であることを示唆した。またNDRG2は、低酸素幹細胞ニッチでの機能にも役割を果たす可能性が示され、がん幹細胞を含めた更なるその制御機構の解明により、新規分子標的薬の開発につながる可能性が示唆された。