Proposed model of a EGFR/Beta-catenin/cyclin D1 signaling pathway in oral cancer

Proposed model of a EGFR/β-catenin/cyclin D1 signaling pathway in oral cancer. EGFR induces phosphorylation of β-catenin (Tyr) and GSK-3β (Ser-9). Phosphorylation of β-catenin (Tyr) leads to its dissociation from membranes. Phosphorylation of GSK-3β (Ser-9) inhibits its kinase activity so that β-catenin is not degraded, but is translocated to the nucleus. In the absence of an EGFR signal, β-catenin target genes are occupied by a repression complex (e.g., HDAC and Suv39h1), and histones in this area are in a compressed status, marked by high level of H3K9 methylation. Following EGFR signal activation, nuclear-translocated β-catenin combines with TCF/LEF transcription factors to recruit coactivators (e.g., CBP, Brg, etc.) to the regulatory element. These replace the repression complexes, leading to decompression of chromatin and high level of histone acetylation and H3K4 methylation.

Publication

Epidermal growth factor receptor regulates β-catenin location, stability, and transcriptional activity in oral cancer. (2010) Chien-Hsing Lee, et al. Mol Cancer. 2010;9:64-64. Figure: F7. All organisms Mus musculus Homo sapiens Capra hircus Canis lupus familiaris Equus asinus Bos taurus Oryctolagus cuniculus Drosophila melanogaster Danio rerio

Disease mentions