Supplementary Data 1-4, Table from Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma

Zhang, Jing; Sattler, Martin; Tonon, Giovanni; Grabher, Clemens; Lababidi, Samir; Zimmerhackl, Alexander; Raab, Marc S.; Vallet, Sonia; Zhou, Yiming; Cartron, Marie-Astrid; Hideshima, Teru; Tai, Yu-Tzu; Chauhan, Dharminder; Anderson, Kenneth C.; Podar, Klaus

doi:10.1158/0008-5472.22378751.v1

Supplementary Data 1-4, Table from Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma

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posted on 2023-03-30, 18:49 authored by Jing Zhang, Martin Sattler, Giovanni Tonon, Clemens Grabher, Samir Lababidi, Alexander Zimmerhackl, Marc S. Raab, Sonia Vallet, Yiming Zhou, Marie-Astrid Cartron, Teru Hideshima, Yu-Tzu Tai, Dharminder Chauhan, Kenneth C. Anderson, Klaus Podar

Supplementary Data 1-4, Table from Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma

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ARTICLE ABSTRACT

Bone marrow angiogenesis is associated with multiple myeloma (MM) progression. Here, we report high constitutive hypoxia-inducible factor-1α (Hif-1α) expression in MM cells, which is associated with oncogenic c-Myc. A drug screen for anti-MM agents that decrease Hif-1α and c-Myc levels identified a variety of compounds, including bortezomib, lenalidomide, enzastaurin, and adaphostin. Functionally, based on transient knockdowns and overexpression, our data delineate a c-Myc/Hif-1α–dependent pathway mediating vascular endothelial growth factor production and secretion. The antiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model and translated into a preclinical in vitro and in vivo model of MM in the bone marrow milieu. Our data, therefore, identify Hif-1α as a novel molecular target in MM and add another facet to anti-MM drug activity. [Cancer Res 2009;69(12):5082–90]

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Angiogenesis Angiogenesis mechanisms Gene Regulation Oncogenic transcription factors Hematological Cancers Myelomas

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Supplementary Data 1-4, Table from Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma

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