title: The twisted survivin connection to angiogenesis.
abstract: 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.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, 8330024, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Sanhueza
authors.affiliation: Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Wehinger
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Castillo Bennett
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Valenzuela
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.|Facultad de Ciencias Biológicas & Center UC Investigation in Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: G I
authors.initials: GI
authors.lastname: Owen
authors.affiliation: 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. aquest@med.uchile.cl.|Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. aquest@med.uchile.cl.
authors.forename: A F G
authors.initials: AF
authors.lastname: Quest
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D017382:Reactive Oxygen Species; D000077022:Survivin