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

Genes and Development - Tập 27 Số 6 - Trang 670-682 - 2013
Christine E. Wong1, Jennifer S. Yu2,3, David A. Quigley1, Minh D. To1, Kuang‐Yu Jen4, Phillips Huang1, Reyno Del Rosario1, Allan Balmain1
11Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94158, USA
22Department of Radiation Oncology,
33Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA
44Department of Pathology, University of California at San Francisco, San Francisco, California 94143, USA

Tóm tắt

Epithelial–mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%–30% ofHrasmutant 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 frequentInk4/Arfdeletions. Deletion ofHrasfrom the mouse germline also leads to a strong reduction in squamous tumor development, but tumors now acquire activatingKrasmutations 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.

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Genes and Development

Tập 27 Số 6

670-682

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