Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 21 June 2011
Vol. 4, Issue 178, p. pt4
[DOI: 10.1126/scisignal.2002072]

PRESENTATIONS

HIF-1α Mediates Tumor Hypoxia to Confer a Perpetual Mesenchymal Phenotype for Malignant Progression

Young-Gun Yoo1, Jared Christensen1, Jie Gu1, and L. Eric Huang1,2*

1 Department of Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA.
2 Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84132, USA.

A presentation from the Keystone Symposium on Epithelial Plasticity and Epithelial-to-Mesenchymal Transition, Vancouver, British Columbia, Canada, 21 to 26 January 2011.

Abstract: 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 1α (HIF-1α) 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-1α 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-1α 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-1α promotes a perpetual mesenchymal phenotype, thereby advancing tumor progression.

* Presenter and corresponding author. E-mail, eric.huang{at}hsc.utah.edu

Citation: Y.-G. Yoo, J. Christensen, J. Gu, L. E. Huang, HIF-1α Mediates Tumor Hypoxia to Confer a Perpetual Mesenchymal Phenotype for Malignant Progression. Sci. Signal. 4, pt4 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
BIBF 1120 (Nintedanib), a Triple Angiokinase Inhibitor, Induces Hypoxia but not EMT and Blocks Progression of Preclinical Models of Lung and Pancreatic Cancer.
B. Kutluk Cenik, K. T. Ostapoff, D. E. Gerber, and R. A. Brekken (2013)
Mol. Cancer Ther. 12, 992-1001
   Abstract »    Full Text »    PDF »
Autophagy Inhibition Sensitizes Colon Cancer Cells to Antiangiogenic and Cytotoxic Therapy.
M. Selvakumaran, R. K. Amaravadi, I. A. Vasilevskaya, and P. J. O'Dwyer (2013)
Clin. Cancer Res. 19, 2995-3007
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882