Loss of Grainy Head-Like 1 Is Associated with Disruption of the Epidermal Barrier and Squamous Cell Carcinoma of the SkinReportar como inadecuado




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The Grainyhead-like 1 GRHL1 transcription factor regulates the expression of desmosomal cadherin desmoglein 1 Dsg1 in suprabasal layers of the epidermis. As a consequence, the epidermis of Grhl1-null mice displays fewer desmosomes that are abnormal in structure. These mice also exhibit mild chronic skin barrier defects as evidenced by altered keratinocyte terminal differentiation, increased expression of inflammatory markers and infiltration of the skin by immune cells. Exposure of Grhl1−-− mice to a standard chemical skin carcinogenesis protocol results in development of fewer papillomas than in wild type control animals, but with a rate of conversion to squamous cell carcinoma SCC that is strikingly higher than in normal littermates. The underlying molecular mechanism differs from mice with conditional ablation of a closely related Grhl family member, Grhl3, in the skin, which develop SCC due to the loss of expression of phosphatase and tensin homolog PTEN and activation of the phosphatidylinositol 3-kinase PI3K-AKT-mechanistic target of rapamycin mTOR signaling pathway.



Autor: Michal Mlacki, Charbel Darido, Stephen M. Jane, Tomasz Wilanowski

Fuente: http://plos.srce.hr/



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