Roles of Girdin phosphorylation by Akt kinase in human diseases

2014 Fiscal Year Final Research Report

• Project Area: Regulation of signal transduction by post-translational modifications and its pathogenic dysregulation
• Project/Area Number: 22117005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya University
• Principal Investigator: TAKAHASHI Masahide 名古屋大学, 医学(系)研究科(研究院), 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): ENOMOTO Atsushi 名古屋大学, 医学系研究科, 准教授 (20432255)
• Co-Investigator(Renkei-kenkyūsha): ASAI Naoya 名古屋大学, 医学系研究科, 准教授 (80273233)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: Girdin / Aktキナーゼ / がんの進展 / がん微小環境 / 網膜血管新生 / 血管内膜肥厚 / 神経新生

Outline of Final Research Achievements

We　found　that　girdin　and　its　phosphorylation　play　important　roles　in cell migration of cancer cells, endothelial cells and neuronal cells. Thus, girdin’s function influences pathophysiology of human diseases such as cancer progression and vascular disease. Girdin is an actin-binding protein and is phosphorylated at serine 1416 by Akt. In this project, we generated knock-in mice in which serine1416 in girdin was replaced with alanine. Using knock-in mice, we demonstrated that Akt-girdin signaling in cancer-associated fibroblasts contributes to tumor progression. In addition, Akt-girdin signaling in vascular smooth muscle cells was shown to be important for neointima formation after vascular injury. We also found that this signaling is crucial for growth and invasion of glioblastoma cells in vitro and in vivo. These findings suggest that Akt-giridin signaling becomes new therapeutic target for treatment of cancer and vascular disease.

Free Research Field

実験病理学