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PNAS 108 (10): 4093-4098

Copyright © 2011 by the National Academy of Sciences.

From the Cover


Wounding mobilizes hair follicle stem cells to form tumors

Sunny Y. Wong Jeremy F. Reiter1

Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158

Edited* by Matthew P. Scott, Stanford University/Howard Hughes Medical Institute, Stanford, CA, and approved November 12, 2010 (received for review September 2, 2010)

Abstract: A wide variety of human cancers are associated with injury. Although stem cells participate in tissue regeneration after wounding, it is unclear whether these cells also contribute to epithelial tumors. Human basal cell carcinomas (BCCs) are associated with misactivation of Hedgehog (Hh) signaling, commonly through acquisition of mutations in Smoothened (Smo). We have found that expression of an activated form of Smo by stem cells of the hair-follicle bulge and secondary hair germ does not induce robust Hh signaling or produce BCCs. However, wounding recruits these cells from the follicle to the wound site, where downstream Hh signal transduction is derepressed, giving rise to superficial BCC-like tumors. These findings demonstrate that BCC-like tumors can originate from follicular stem cells and provide an explanation for the association between wounding and tumorigenesis.

Key Words: skin cancer • wound healing • carcinogenesis • reepithelialization

Author contributions: S.Y.W. designed research; S.Y.W. performed research; S.Y.W. and J.F.R. analyzed data; S.Y.W. and J.F.R. wrote the paper.

The authors declare no conflict of interest.

*This Direct Submission article had a prearranged editor.

This article contains supporting information online at

1To whom correspondence should be addressed. E-mail: jeremy.reiter{at}

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