Format

Send to

Choose Destination
See comment in PubMed Commons below
Genes Dev. 2013 Mar 15;27(6):670-82. doi: 10.1101/gad.210427.112.

Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression.

Author information

1
Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94158, USA.

Abstract

Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic inflammation causes a dramatic reduction in classical papillomas and squamous cell carcinomas (SCCs), but the mice still develop highly invasive carcinomas with EMT properties, reduced levels of Hras and Egfr signaling, and frequent Ink4/Arf deletions. Deletion of Hras from the mouse germline also leads to a strong reduction in squamous tumor development, but tumors now acquire activating Kras mutations and exhibit more aggressive metastatic properties. We propose that invasive carcinomas can arise by different genetic and biological routes dependent on exposure to chronic inflammation and possibly from different target cell populations within the skin. Our data have implications for the use of inhibitors of inflammation or of Ras/Egfr pathway signaling for prevention or treatment of invasive cancers.

PMID:
23512660
PMCID:
PMC3613613
DOI:
10.1101/gad.210427.112
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center