HIF-1? mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progression

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Publication Type journal article
School or College School of Medicine
Department Neurosurgery; Oncological Sciences
Creator Huang, Lin Eric
Other Author Yoo, Young Gun; Christensen, Jared; Gu, Jie
Title HIF-1? mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progression
Description Although tumor progression involves genetic and epigenetic alterations to normal cellular biology, the underlying mechanisms of these changes remain obscure. Numerous studies have shown that hypoxia-inducible factor 1? (HIF-1?) is overexpressed in many human cancers and up-regulates a host of hypoxia-responsive genes for cancer growth and survival. We recently identified an alternative mechanism of HIF-1? function that induces genetic alterations by suppressing DNA repair. Here, we show that long-term hypoxia, which mimics the tumor microenvironment, drives a perpetual epithelial-mesenchymal transition (EMT) through up-regulation of the zinc finger E-box binding homeobox protein ZEB2, whereas short-term hypoxia induces a reversible EMT that requires the transcription factor Twist1. Moreover, we show that the perpetual EMT driven by chronic hypoxia depends on HIF-1? induction of genetic alterations rather than its canonical transcriptional activator function. These mesenchymal tumor cells not only acquire tumorigenicity but also display characteristics of advanced cancers, including necrosis, aggressive invasion, and metastasis. Hence, these results reveal a mechanism by which HIF-1? promotes a perpetual mesenchymal phenotype, thereby advancing tumor progression. REPRINT REQUEST LINK: <http://stke.sciencemag.org/cgi/content/full/sigtrans;4/178/pt4?ijkey=/7ZMa8FsAuw0I&keytype=ref&siteid=sigtrans>
Type Text
Publisher American Association for the Advancement of Science
Language eng
Bibliographic Citation Y.-G. Yoo, J. Christensen, J. Gu, L. E. Huang, HIF-1? Mediates Tumor Hypoxia to Confer a Perpetual Mesenchymal Phenotype for Malignant Progression. Sci. Signal. 4, pt4 (2011). <http://stke.sciencemag.org/cgi/content/full/sigtrans;4/178/pt4?ijkey=/7ZMa8FsAuw0I&keytype=ref&siteid=sigtrans>
Rights Management (c)American Association for the Advancement of Science
Format Medium application/html
Source Science Signaling. 21 June 2011 Vol. 4, Issue 178, p. pt4
ARK ark:/87278/s6kd2gmj
Setname ir_uspace
Date Created 2012-07-30
Date Modified 2012-07-30
ID 707696
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kd2gmj
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