Identification of hypoxia induced factor relating to cancer stemness and treatment resistance.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861185
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: UEMURA Mamoru 大阪大学, 医学(系)研究科(研究院), 助教 (10528483)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 大腸癌 / 低酸素 / JMJD1A / 低プロテアソーム活性 / 癌幹細胞 / 治療抵抗性 / EMT / 予後因子

Outline of Final Research Achievements

In colorectal cancer cells, JMJD1A induced EMT, chemotherapy resistant ability, and aggressive invasion ability under hypoxic condition. ChIP assay using JMJD1A antibody revealed that histone modification caused activation of EMT inducers. JMJD1A induced EMT under a hypoxic condition and it may enhance drug resistance in CRC. Silencing JMJD1A may be an efficient molecular-targeted cancer therapy.
LPACs (low proteasome activity cells) of CRC cells had significant radioresistance and chemoresistance (5-FU and oxaliplatin). Cancer stemness of LPACs was confirmed by CSC marker, sphere formation assay, ROS activity analysis, cell cycle assay, and in vivo tumorigenicity examination. Microarray analysis identified EID3 (EP300 Interacting Inhibitor of Differentiation 3) as a key factor related to treatment resistance of LPACs. Functional analyses of EID3 and analysis using clinical samples confirmed the role of EID3 in LPACs.

Free Research Field

消化器外科