Endogenous Myc maintains the tumor microenvironment
- Nicole M. Sodir1,2,
- Lamorna Brown Swigart1,2,
- Anthony N. Karnezis1,2,
- Douglas Hanahan3,
- Gerard I. Evan1,2,4,6 and
- Laura Soucek1,2,5
- 1Department of Pathology, University of California at San Francisco, San Francisco, California 94143, USA;
- 2Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143, USA;
- 3Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Federale Lausanne, The Swiss Federal Institute of Technology, Lausanne CH-1015, Switzerland;
- 4Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom
Abstract
The ubiquitous deregulation of Myc in human cancers makes it an intriguing therapeutic target, a notion supported by recent studies in Ras-driven lung tumors showing that inhibiting endogenous Myc triggers ubiquitous tumor regression. However, neither the therapeutic mechanism nor the applicability of Myc inhibition to other tumor types driven by other oncogenic mechanisms is established. Here, we show that inhibition of endogenous Myc also triggers ubiquitous regression of tumors in a simian virus 40 (SV40)-driven pancreatic islet tumor model. Such regression is presaged by collapse of the tumor microenvironment and involution of tumor vasculature. Hence, in addition to its diverse intracellular roles, endogenous Myc serves an essential and nonredundant role in coupling diverse intracellular oncogenic pathways to the tumor microenvironment, further bolstering its credentials as a pharmacological target.
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Footnotes
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↵6 Corresponding author.
E-MAIL gie20{at}cam.ac.uk; FAX (415) 514-0878.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.2038411.
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Supplemental material is available for this article.
- Received February 2, 2011.
- Accepted March 15, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
