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

Autor: Allan Balmain, Reyno Del Rosario, Christine E. Wong, Jennifer S. Yu, Minh D. To, Phillips Y. Huang, Kuang-Yu Jen, David A. Quigley
Rok vydání: 2013
Předmět:
Genetic Markers
Epithelial-Mesenchymal Transition
Skin Neoplasms
Cell
Gene Dosage
Inflammation
Biology
medicine.disease_cause
Medical and Health Sciences
Metastasis
Proto-Oncogene Proteins p21(ras)
Hras
Mice
stem cells
Genetics
medicine
2.1 Biological and endogenous factors
Animals
Epithelial–mesenchymal transition
HRAS
Aetiology
Cancer
Cyclin-Dependent Kinase Inhibitor Proteins
Neoplastic
skin carcinogenesis
Gene Expression Profiling
Carcinoma
Psychology and Cognitive Sciences
EMT
Biological Sciences
medicine.disease
ErbB Receptors
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Squamous Cell
Gene Expression Regulation
Mutation
Carcinoma
Squamous Cell
Cancer research
KRAS
medicine.symptom
Stem cell
Signal transduction
Signal Transduction
Research Paper
Developmental Biology
Zdroj: Genes & development, vol 27, iss 6
ISSN: 1549-5477
0890-9369
DOI: 10.1101/gad.210427.112
Popis: 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.
Databáze: OpenAIRE
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