Advanced search
1 file | 4.46 MB Add to list

Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential

Bram De Craene (UGent) , Geertrui Denecker (UGent) , Petra Vermassen (UGent) , Joachim Taminau (UGent) , C Mauch, Annie Derore (UGent) , J Jonkers, E Fuchs and Geert Berx (UGent)
(2014) CELL DEATH AND DIFFERENTIATION. 21(2). p.310-320
Author
Organization
Abstract
Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.
Keywords
TRANSCRIPTION FACTOR SNAIL, EPITHELIAL-MESENCHYMAL TRANSITION, Snail, EMT, skin cancer, stem cells, STEM-CELLS, E-CADHERIN, HAIR FOLLICLE, TUMOR RECURRENCE, REPRESSOR SNAIL, DIFFERENTIATION, KERATINOCYTES, PROTEIN

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 4.46 MB

Citation

Please use this url to cite or link to this publication:

MLA
De Craene, Bram, Geertrui Denecker, Petra Vermassen, et al. “Epidermal Snail Expression Drives Skin Cancer Initiation and Progression Through Enhanced Cytoprotection, Epidermal Stem/progenitor Cell Expansion and Enhanced Metastatic Potential.” CELL DEATH AND DIFFERENTIATION 21.2 (2014): 310–320. Print.
APA
De Craene, Bram, Denecker, G., Vermassen, P., Taminau, J., Mauch, C., Derore, A., Jonkers, J., et al. (2014). Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential. CELL DEATH AND DIFFERENTIATION, 21(2), 310–320.
Chicago author-date
De Craene, Bram, Geertrui Denecker, Petra Vermassen, Joachim Taminau, C Mauch, Annie Derore, J Jonkers, E Fuchs, and Geert Berx. 2014. “Epidermal Snail Expression Drives Skin Cancer Initiation and Progression Through Enhanced Cytoprotection, Epidermal Stem/progenitor Cell Expansion and Enhanced Metastatic Potential.” Cell Death and Differentiation 21 (2): 310–320.
Chicago author-date (all authors)
De Craene, Bram, Geertrui Denecker, Petra Vermassen, Joachim Taminau, C Mauch, Annie Derore, J Jonkers, E Fuchs, and Geert Berx. 2014. “Epidermal Snail Expression Drives Skin Cancer Initiation and Progression Through Enhanced Cytoprotection, Epidermal Stem/progenitor Cell Expansion and Enhanced Metastatic Potential.” Cell Death and Differentiation 21 (2): 310–320.
Vancouver
1.
De Craene B, Denecker G, Vermassen P, Taminau J, Mauch C, Derore A, et al. Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential. CELL DEATH AND DIFFERENTIATION. 2014;21(2):310–20.
IEEE
[1]
B. De Craene et al., “Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential,” CELL DEATH AND DIFFERENTIATION, vol. 21, no. 2, pp. 310–320, 2014.
@article{4295476,
  abstract     = {{Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.}},
  author       = {{De Craene, Bram and Denecker, Geertrui and Vermassen, Petra and Taminau, Joachim and Mauch, C and Derore, Annie and Jonkers, J and Fuchs, E and Berx, Geert}},
  issn         = {{1350-9047}},
  journal      = {{CELL DEATH AND DIFFERENTIATION}},
  keywords     = {{TRANSCRIPTION FACTOR SNAIL,EPITHELIAL-MESENCHYMAL TRANSITION,Snail,EMT,skin cancer,stem cells,STEM-CELLS,E-CADHERIN,HAIR FOLLICLE,TUMOR RECURRENCE,REPRESSOR SNAIL,DIFFERENTIATION,KERATINOCYTES,PROTEIN}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{310--320}},
  title        = {{Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential}},
  url          = {{http://dx.doi.org/10.1038/cdd.2013.148}},
  volume       = {{21}},
  year         = {{2014}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: