β-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells

Abstract

The article presents the data on the structure and mechanisms of β-сatenin functioning. The basic aspects of the role of β-сatenin in malignant transformation have been studied at various tumors. Primary structure of β-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al. This interaction is the base for β-catenin's intracellular multifunctioning. The review presents data on the participation of β-catenin in the mechanisms of adhesion, regulation of RNA metabolism, formation contacts with the cytoskeleton and its role in the canonical Wnt signaling pathway, marked examples pro-inflammatory and anti-inflammatory effects of β-catenin. The β-catenin involvement in malignant transformation and progression of certain tumors is not in doubt. The data on the changes in β-catenin expression in the given examples of colon cancer, prostate cancer, different forms of thyroid cancer and hepatocellular carcinoma are presented with the prospects of its use as a marker and a predictor of malignant transformation. Continued research in this area will not only make use of β-catenin as a potential predictor of malignant tumors, but also to develop approaches to targeted therapy.

Tetrahedral DNA Nanostructure: A Potential Promoter for Cartilage Tissue Regeneration via Regulating Chondrocyte Phenotype and Proliferation

“…We can draw the conclusion from statistical analysis that the expression of these genes was upregulated significantly (β‐catenin was as high as 1.48‐fold, Lef‐1 was 1.79‐fold, Figure a). β‐catenin is an essential positive mediator of Wnt/β‐catenin pathway signaling . When β‐catenin accumulated in the cytoplasm, β‐catenin would be translocated into the nucleus and interacted with Lef‐1.These biological behavior could subsequently regulate the proliferation of cells.…”

Markers of Cancer Cell Invasion: Are They Good Enough?

“…E-cadherin, which forms adherens junctions in an epithelial cell layer, is repressed by Snail, Slug, and Twist transcription factors during EMT [64]. The loss of E-cadherin and the nuclear localization of β-catenin, involved in signaling to the actin cytoskeleton [118], were observed in tumor cells at the invasive front in various cancers [69]. Nuclear accumulation of β-catenin in tumor cells in the invasive front and in vessels was found to be a powerful predictor of liver metastasis in colorectal cancer [70,71].…”

Markers of the Epithelial-Mesenchymal Transition in Cells of Endometrial Carcinoma

“…These translocations of E-cadherin and β-catenin can occur during activation of various signaling cascades (TGFβ, FGF and Wnt), and due to disorders in the functioning of the genes of CDH1, CTNND1 or genes that provide degradation of β-catenin (e.g., APC gene) [13,14]. In a nucleus, a transcriptional complex formed between β-catenin and T-cell-and lymphoid factors (TCF LEF) activates the expression of a number of target genes, including the C-MYC, CCND1, VEGF, Axin-2, Snail, VIM and others, which leads to an increase in proliferative and angiogenic potential of malignant neoplasms, which is accompanied by the appearance of a marker of the mesenchymal tissues vimentin [13,14,16,19].…”

“…E-cadherin belongs to the family of transmembrane glycoproteins being one of the key cadherins that provides Ca 2+ -dependent homophilic adhesion in epithelial tissues by the formation of transdimers in two adjacent cells via the interaction of extracellular domains [12]. Its intracellular domain is bound to a number of proteins and, in the first place, with β-catenin, which, apart from E-cadherin, binds with α-catenin and actin microfilaments, providing dense intercellular contacts [12,13]. The interaction of E-cadherin with β-catenin is regulated Submitted: September 04, 2018.…”

“…In addition, the functional loss of E-cadherin may be due to the activation of transcription factors Snail1 and Snail2 or ZEB1 and ZEB2, which suppress the expression of the CDH1 gene [14,19]. As a result, the destruction of E-cadherin/β-catenin complex and intercellular bonds occurs, E-cadherin is translocated into the cytoplasm, and β-catenin is released and accumulated in the cytoplasm followed by its translocation into the nucleus [13,14].…”