Fiche du document
2012
- doi: 10.1016/j.cell.2012.03.048
- issn: 0092-8674
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2012.03.048
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/22682244
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1097-4172
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_C13437B7972C3
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Tumours Neoplasms Integument (Skin) Cutis Carcinoma Cancers Malignancy (Cancer) Malignant tumorsCiter ce document
B. Hu et al., « Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. », Serveur académique Lausannois, ID : 10.1016/j.cell.2012.03.048
Métriques
Partage / Export
Résumé
It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through upregulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix-remodeling enzymes. In human skin samples, stromal fields adjacent to multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer.