β-Catenin is a multifunctional protein with a central role in physiological homeostasis. Its aberrant high expression leads to various diseases including cancer. β-Catenin is the mammalian homologue of the drosophila armadillo gene. It acts both as a transcriptional co-regulator and an adaptor protein for intracellular adhesion. Wnt is the chief regulator of β-catenin, which is a family of 19 glycoproteins to regulate both the β-catenin-dependent (canonical Wnt) and -independent (non-canonical Wnt) signaling pathways. In canonical Wnt pathway, Dsh, β-catenin, Glycogen Synthase Kinase 3 beta (GSK3β), adenomatous polyposis coli (APC), AXIN, and T-cell factor (TCF)/lymphoid enhancement factor (LEF) have been identified as signal transducers of the canonical Wnt pathway, in which β-catenin is a core molecule. In the absence of Wnt ligands, β-catenin is kept at a low level through the ubiquitin proteasome system (UPS). 
β-Catenin is recruited into a destruction complex that contains APC and AXIN, which facilitates the phosphorylation of β-catenin by casein kinase 1 (CK1) and then GSK3β. This leads to the ubiquitylation and proteasomal degradation of β-catenin. Upon Wnt activation or genetic mutations of Wnt components, β-catenin accumulates in the cytoplasm and then translocates into the nucleus. Consequently, it binds to LEF-1/TCF4 and some other co-regulators to promote the transcription of target genes such as Jun, c-Myc and CyclinD-1 in a tissue specific manner, most of which encode oncoproteins. In more than half of all cancer cases, such as colorectal carcinoma, breast cancer, liver carcinoma, melanoma and leukemia, β-catenin accumulates within the nucleus or cytoplasm.


1.Shuang Shang,et al. Oncotarget. 2017 May 16; 8(20): 33972–33989.