Functions of a novel hypoxia-inducible reprogramming factor GLIS1 in cancer cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K11252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Tanimoto Keiji 広島大学, 原爆放射線医科学研究所, 助教 (90335688)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: がん / 低酸素 / 遺伝子 / がん幹細胞 / がん細胞分化

Outline of Final Research Achievements

GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression and its function remain unclear. We previously demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions by HIF-2α cooperating with AP-1 family members in cancer cells. We thus conducted this study to analyze GLIS1 functions in cancer cells. As results of functional analyses by using GLIS1-overexpressing cells or inhibition with siRNA, GLIS1 was found to inhibit cell proliferation, but increase cell migration and sphere formation capacity in cancer cells. Comprehensive gene expression analyses indicated that GLIS1 regulated tissue remodeling, EMT, adipogenesis, glycolysis, and so on. Further inhibitor of DNA methylation (5-azaC) treatment increased expressions of GLIS1 in various cancer cell lines, suggesting epigenetic regulation in cancer cells.

Free Research Field

分子腫瘍学