The twisted survivin connection to angiogenesis

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Survivin, an inhibitor of apoptosis protein (IAP), is overexpressed in most human cancers.
• Its role in cell division, apoptosis, metastasis, and angiogenesis makes it a potential cancer treatment target.

Purpose of the Study:

• To discuss recent findings on survivin expression regulation and its role in angiogenesis, especially under hypoxia.
• To propose a novel role for survivin in promoting VEGF synthesis, secretion, and angiogenesis in cancer cells.

Main Methods:

• Review of recent findings on survivin regulation and function.
• Mechanistic proposal involving PI3-kinase/Akt and β-Catenin-TCF/LEF pathways.
• Discussion of survivin's contribution to tumor vascularization.

Main Results:

• Survivin expression in tumor cells promotes VEGF synthesis and secretion.
• A positive feedback loop involving PI3-kinase/Akt activation enhances VEGF expression.
• This mechanism contributes to tumor vascularization via angiogenesis and vasculogenic mimicry.

Conclusions:

• Survivin plays a novel role in promoting tumor angiogenesis through VEGF.
• A PI3-kinase/Akt and β-Catenin-TCF/LEF dependent feedback loop regulates VEGF expression.
• Survivin-mediated mechanisms enhance tumor vascularization, impacting cancer progression.