β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus.

In the canonical Wnt cascade, β-catenin is the key effector responsible for transduction of the signal to the nucleus and it triggers transcription of Wnt-specific genes responsible for the control of cell fate decisions in many cells and tissues.

This protein is present in many types of cells and tissues, where it is primarily found at junctions that connect neighboring cells (adherens junctions). Beta-catenin plays an important role in sticking cells together (cell adhesion) and in communication between cells.

Mechanistically, Wnt/β-catenin signaling pathway upregulates the expression of cell cycle-related proteins, such as Cyclin B1 and Cyclin C to promote carcinogenesis and development of HCC [89]. When talking about tumor growth, Wnt/β-catenin signaling may play opposing roles in different tumor tissues.

β-Catenin activation is associated with increased cytotrophoblast invasion in response to a variety of cellular stimuli. However, whether β-catenin activation directly causes enhanced invasiveness of cytotrophoblast cells or is a consequence of differentiation to a more invasive lineage is not yet known.

β-catenin target genes have been implicated in regulating different cellular processes including proliferation (e.g., MYC, CCND1, PPARD), stem cell fate (ASCL2), survival (ABCB1, BIRC5), differentiation (ID2, ITF2, ENC1), migration (MMP7, MMP14), and angiogenesis (VEGF) [4–18].

Wnt proteins are secreted, lipid-modified glycoproteins that allow for communication between cells. They regulate cell growth, function, differentiation, and cell death. Wnt proteins play a central role in bone development, modeling, and remodeling.

Canonical pathway The canonical Wnt pathway (or Wnt/β-catenin pathway) is the Wnt pathway that causes an accumulation of β-catenin in the cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of transcription factors that belong to the TCF/LEF family.

Functional assays indicate that β-catenin plays a key role in the development of the endoderm. Similarly, over-expression of the cytoplasmic domain of cadherin or a β-catenin-engrailed repressor fusion construct prevented endoderm formation and generated the same animalized phenotype.

In the absence of Wnt signaling, cytosolic β-catenin is rapidly degraded through the ubiquitin–proteosome system. Removal of β-catenin from Tcf/DNA complexes allows the transcriptional corepressor Groucho to access Tcfs and repress transcription of Wnt targets (Cavallo et al., 1998; Roose et al., 1998).

Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal.

Additional catenins such as γ-catenin and δ-catenin have been identified. The name “catenin” was originally selected (‘catena’ means ‘chain’ in Latin) because it was suspected that catenins might link cadherins to the cytoskeleton.

Catenin beta-1, also known as β-catenin, is a protein that in humans is encoded by the CTNNB1 gene . β-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription. In humans, the CTNNB1 protein is encoded by the CTNNB1 gene.

There are two types: β-catenin, which is linked to the cadherin itself and α-catenin, which associates with actin microfilaments. A gene on chromosome 17q21 that encodes a major cytoplasmic protein common to both submembranous plaques of desmosomes and intermediate junctions.

Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as α-catenin and β-catenin. A-catenin can bind to β-catenin and can also bind actin. B-catenin binds the cytoplasmic domain of some cadherins.