Regulation of tumor angiogenesis by integrin-linked kinase (ILK)

Speaker:陳俊成                              Time:2004/3/2414:00~15:00

Commentator:周楠華老師                      Place:Room 601

Abstract

Angiogenesis, the development of new blood vessels from pre-existing vasculature, plays a critical role in cancer progression. In the case of cancer, angiogenesis is essential for the growth, progression, and metastasis of a tumor and, thus, inhibition of angiogenesis is attractive therapeutic option. One of the key mediators of angiogenesis is vascular endothelial cell growth factor (VEGF), which can promote the proliferation, survival, and migration of endothelial cells and is essential for blood vessel formation. A major transcriptional activator of the VEGF gene is hypoxia-inducible factor-1α (HIF-1α). Recent studies indicate that the expression of VEGF via the activation of thephosphatidylinositol 3-kinase (PI-3 kinase) signaling has also been shown to be mediated by HIF-1α. Integrin-linked kinase (ILK), a component of the PI-3 kinase pathway and an upstream regulator of the phosphorylation of PKB/Akt, also promotes cell migration and invasion. In this paper, the authors investigated whether ILK is involved in the stimulation of VEGF expression in tumor cells and whether ILK is required for VEGF-mediated endothelial cell migration and formation of blood vessels. Overexpression of ILK stimulated VEGF expression in a PKB/Akt- and HIF-1α- dependent manner；inhibition of ILK activity by pharmacological inhibitor or siRNA resulted in inhibition of VEGF- stimulated angiogenesis, decreasing of Akt/PKB and mTOR/FRAP phosphorylation, inhibition of tumor angiogenesis and suppression of tumor growth in ILK inhibitor-treated PC3 xenograft tumor model. Consequently, ILK plays important roles in two key aspects of tumor angiogenesis: VEGF expression by tumor cells and VEGF-stimulated blood vessel formation. Therefore, ILK may be a promising therapeutic target for the inhibition of tumor angiogenesis.

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