Vasohibin-1 signaling mechanism

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology; General physiology
• Research Institution: Tohoku University
• Principal Investigator: KOBAYASHI Miho 東北大学, 加齢医学研究所, 助教 (50630539)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 血管新生 / Vasohibin-1 / VEGF

Outline of Final Research Achievements

Major target of anti-cancer therapy is VEGF, but its therapeutic approach gave several issues such as a switching to other angiogenic factors from VEGF, and causes vessel disorder in other normal tissue. Vasohibin-1 (VASH1) is a VEGF- or FGF2-inducible anti-angiogenic factor that plays a role of negative feedback regulator on angiogenesis by broad angiogenic factors. VASH1 potently induces increase in detyrosination of α-tubulin in endothelial cells (ECs). This study revealed that VASH1 simultaneously induced Glu-tubulin increment, inhibition of VEGF-signaling, VEGF-inducible ECs migration and network formation. Co-expression of TTL (tubulin tyrosine ligase), normalized the level of Glu-tubulin, and abrogated the VASH1-induced suppression both of VEGF-signaling and VEGF-induced angiogenesis. Thus, I propose that VASH1 induces inhibition of VEGF-signaling and angiogenesis through the bias of a tubulin tyrosination/detyrosinatin cycle.

Free Research Field

分子細胞生物学