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

Christine E. Wong, Jennifer S. Yu, David A. Quigley, Minh D. To, Kuang-Yu Jen, Phillips Y. Huang, Reyno Del Rosario, Allan Balmain

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)670-682
Number of pages13
JournalGenes and Development
Volume27
Issue number6
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

Keywords

  • EMT
  • Hras
  • Inflammation
  • Skin carcinogenesis
  • Stem cells

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Wong, C. E., Yu, J. S., Quigley, D. A., To, M. D., Jen, K-Y., Huang, P. Y., Del Rosario, R., & Balmain, A. (2013). Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression. Genes and Development, 27(6), 670-682. https://doi.org/10.1101/gad.210427.112