Conditional ablation of p130Cas/BCAR1 adaptor protein impairs epidermal homeostasis by altering cell adhesion and differentiation
| Autor: | Beatrice Tassone, Sara Cabodi, Aurora Dadone, Emilia Turco, Andrea Costamagna, Matilde Simoni, Paola Defilippi, Enzo Calautti, Marianna Sciortino, Stefania Saoncella, Dora Natalini, Maria del Pilar Camacho Leal |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Mouse primary keratinocytes lcsh:Medicine Biochemistry Extracellular matrix 03 medical and health sciences chemistry.chemical_compound Adaptor proteins Cell adhesion Cell signaling and cell differentiation Progenitor cell lcsh:QH573-671 Molecular Biology Chemistry Cell growth lcsh:Cytology lcsh:R Tyrosine phosphorylation Cell Biology Cell biology 030104 developmental biology Catenin BCAR1 Crk-Associated Substrate Protein |
| Zdroj: | Cell Communication and Signaling, Vol 16, Iss 1, Pp 1-13 (2018) |
| DOI: | 10.1186/s12964-018-0289-z |
| Popis: | Background p130 Crk-associated substrate (p130CAS; also known as BCAR1) is a scaffold protein that modulates many essential cellular processes such as cell adhesion, proliferation, survival, cell migration, and intracellular signaling. p130Cas has been shown to be highly expressed in a variety of human cancers of epithelial origin. However, few data are available regarding the role of p130Cas during normal epithelial development and homeostasis. Methods To this end, we have generated a genetically modified mouse in which p130Cas protein was specifically ablated in the epidermal tissue. Results By using this murine model, we show that p130Cas loss results in increased cell proliferation and reduction of cell adhesion to extracellular matrix. In addition, epidermal deletion of p130Cas protein leads to premature expression of “late” epidermal differentiation markers, altered membrane E-cadherin/catenin proteins localization and aberrant tyrosine phosphorylation of E-cadherin/catenin complexes. Interestingly, these alterations in adhesive properties in absence of p130Cas correlate with abnormalities in progenitor cells balance resulting in the amplification of a more committed cell population. Conclusion Altogether, these results provide evidence that p130Cas is an important regulator of epidermal cell fate and homeostasis. |
| Databáze: | OpenAIRE |
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