%0 Journal Article
%T Interaction between Wnt/¦Â-catenin and RAS-ERK pathways and an anti-cancer strategy via degradations of ¦Â-catenin and RAS by targeting the Wnt/¦Â-catenin pathway
%A Eun Ji Ro
%A Kang-Yell Choi
%A Woo-Jeong Jeong
%J Archive of "NPJ Precision Oncology".
%D 2018
%R 10.1038/s41698-018-0049-y
%X The canonical Wnt/¦Â-catenin pathway. a In the absence of Wnt ligands, APC (adenomatous polyposis coli) and Axin are recruited into the ¡°¦Â-catenin destruction complex¡±. The phosphorylations by CK1¦Á (casein kinase 1¦Á) and GSK3¦Â (glycogen synthase kinase 3¦Â) recruit ¦Â£¿TrCP E3 linker (¦Â-transducin repeat-containing protein, an E3 ubiquitin ligase), and subsequently degrade ¦Â£¿catenin via the proteasome. Low-cytoplasmic levels of ¦Â-catenin ensure in activation of TCF/LEF (T-cell factor/lymphoid enhancer factor) transcription factors and transcriptional repression of Wnt target genes. b In the accumulation of the extracellular Wnt ligands, the association of Axin with phosphorylated LRP5/6 (lipoprotein receptor-related protein 5/6) and recruitment of phosphorylated DVL (dishevelled) to FZD (frizzled) lead to the dissociation of the destruction complex. ¦Â-Catenin is stabilized, translocated into the nucleus, forms the complex with TCF or LEF, and subsequently activates the target genes. CCND1, cyclin D1; EGFR, epidermal growth factor receptor; LGR5, Leucine-rich repeat-containing G-protein coupled receptor 5; P, phosphorylation; U, ubiquitinatio
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871897/