Elsevier

Oral Oncology

Volume 50, Issue 9, September 2014, Pages 818-824
Oral Oncology

β-Catenin in oral cancer: An update on current knowledge

https://doi.org/10.1016/j.oraloncology.2014.06.005Get rights and content

Summary:

β-Catenin is a multiple function protein. These functions derive from its interactions with other cell proteins, both on the cell membrane, in the cytoplasm and in the nucleus. β-Catenin forms a complex with the adhesion molecule E-cadherin, promoting cell–cell adhesion and thereby preventing the cell dissociation that is required for cancer invasion and progression mechanisms. There is also a dynamic pool of cytoplasmic β-catenin that serves as connection between the extracellular microenvironment and the nucleus. Cytoplasmic β-catenin acts as a transcription factor for the nucleus in the canonical Wnt pathway, activating the transcription of various genes. Structural or functional alterations of β-catenin can promote cancer progression. This review addresses the current knowledge on the implications of β-catenin in the development of oral cancer.

Introduction

β-Catenin is a protein of the Armadillo family, and it has multiple functions that depend on its cellular localization. These functions derive from its interactions with other cellular proteins, both on the membrane and in the cytoplasm and nucleus, made possible by the presence in the molecule of a central repetitive domain [1], [2] that acts as common platform to create functional complexes with other proteins (Fig. 1).

β-Catenin forms a complex with the adhesion molecule E-cadherin, promoting cell–cell adhesion and contributing to the structural formation of the stratified squamous epithelium of the oral mucosa, also preventing the cell dissociation required for cancer invasion and progression. Besides the membrane localization, there is a dynamic pool of cytoplasmic β-catenin that serves as rapid connection between the extracellular microenvironment and nucleus through the plasma membrane [3]. Thus, cytoplasmic β-catenin acts as signal transcription factor to the nucleus in the canonical Wnt pathway, activating the transcription of genes with various cell functions [2]. Over the past few years, it has been confirmed that structural or functional alterations of β-catenin, or of the molecules with which it interacts, can promote cancer progression, either by increasing cell mobility and invasiveness secondary to the loss of cell adhesive functions, or by promoting oncogene transcription linked to a dysregulation of the canonical Wnt pathway. This review addresses the current knowledge on the implications of β-catenin in the development of oral cancer.

Section snippets

Functions of β-catenin

β-Catenin is usually located in the cell membrane, forming complexes with the adhesion molecule E-cadherin.

Oncogenic mechanisms linked to β-catenin

The cellular localization of β-catenin is an important indirect indicator of its oncogenic activity (Fig. 2). One oncogenic mechanism linked to β-catenin is relates to the loss of its adhesive function when localized on the cell membrane or to its translocation to the nucleus, where it acts as a transcription factor for different oncogenes [44]. It is therefore important to establish the topographic localization of β-catenin cellular expression in order to understand the oncogenic mechanisms.

Potential therapeutic implications

Despite the oncogenic activity of β-catenin being well-documented, there have been remarkably few attempts to manipulate it. Thus, there have been studies with molecules such as Chibby [3] and Tax-Interaction Protein-1 (TIP-1), which inhibit the interaction between β-catenin and TCF but these have been inadequate to control the high levels of stabilized β-catenin seen in cancerous cells [2]. Other small β-catenin/TCF4-inhibitor molecules have been found to lack specificity though have also

Conflict of interest statement

None declared.

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