Epigenetic regulation of ANGPTL2 expression in cancer and lifestyle disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870543
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry; Tumor diagnostics
• Research Institution: Kumamoto University
• Principal Investigator: KADOMATSU Tsuyoshi 熊本大学, 大学院生命科学研究部, 助教 (90555757)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 癌 / 生活習慣病 / エピゲノム / 発現制御 / ANGPTL2

Outline of Final Research Achievements

We showed that the tumor microenvironment, such as hypoxia and nutrient starvation, increased ANGPTL2 expression levels in osteosarcoma cells and decreased DNA methylation levels of its promoter. In addition, the tumor microenvironment induced expression of DNA demethylation-related enzymes in osteosarcoma cells. These results suggest that the tumor microenvironment induces ANGPTL2 expression in tumor cells by inducing DNA demethylation of its promoter. We also showed that tumor cell-derived ANGPTL2 enhanced tumor metastasis through promoting invasive activity of tumor cells and tumor cell intravasation. Furthermore, We found that full-length ANGPTL2 protein was extracellularly cleaved by TLL1 into an inactive form lacking the capacity to enhance tumor aggressiveness. Thus, strategies to promote cleavage of full-length ANGPTL2 by TLL1 could block metastasis.

Free Research Field

分子遺伝学