The twisted survivin connection to angiogenesis

Molecular Cancer

Review

G. I. Owen¹  J. Castillo Bennett²  M. Valenzuela²  A. F. G. Quest²  C. Sanhueza³  S. Wehinger⁴ 

[1] Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile;Facultad de Ciencias Biológicas & Center UC Investigation in Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile;Cellular Communication Laboratory, Center for Molecular Studies of the Cell (CEMC), Program of Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Av. Independencia 1027, Santiago, Chile;Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile;Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024, Santiago, Chile;Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile;

关键词: Survivin;    Hypoxia;    Cell survival;    ROS;    VEGF;    Angiogenesis;    Oxidative stress;    Cancer;   

DOI  :  10.1186/s12943-015-0467-1

 received in 2015-07-06, accepted in 2015-11-08,  发布年份 2015

来源: Springer

【 摘 要 】

Survivin, a member of the inhibitor of apoptosis family of proteins (IAPs) that controls cell division, apoptosis, metastasis and angiogenesis, is overexpressed in essentially all human cancers. As a consequence, the gene/protein is considered an attractive target for cancer treatment. Here, we discuss recent findings related to the regulation of survivin expression and its role in angiogenesis, particularly in the context of hypoxia. We propose a novel role for survivin in cancer, whereby expression of the protein in tumor cells promotes VEGF synthesis, secretion and angiogenesis. Mechanistically, we propose the existence of a positive feed-back loop involving PI3-kinase/Akt activation and enhanced β-Catenin-TCF/LEF-dependent VEGF expression followed by secretion. Finally, we elaborate on the possibility that this mechanism operating in cancer cells may contribute to enhanced tumor vascularization by vasculogenic mimicry together with conventional angiogenesis.

【 授权许可】

CC BY   
© Sanhueza et al. 2015