| First Author | Hu B | Year | 2012 |
| Journal | Cell | Volume | 149 |
| Issue | 6 | Pages | 1207-20 |
| PubMed ID | 22682244 | Mgi Jnum | J:186161 |
| Mgi Id | MGI:5431144 | Doi | 10.1016/j.cell.2012.03.048 |
| Citation | Hu B, et al. (2012) Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling. Cell 149(6):1207-20 |
| abstractText | 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-Jkappa, 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. |
