β-Catenin: oncogenic role and therapeutic target in cervical cancer

Abstract

Cervical cancer is a common and fatal malignancy of the female reproductive system. Human papillomavirus (HPV) is the primary causal agent for cervical cancer, but HPV infection alone is insufficient to cause the disease. Actually, most HPV infections are sub-clinical and cleared spontaneously by the host immune system; very few persist and eventually develop into cervical cancer. Therefore, other host or environmental alterations could also contribute to the malignant phenotype. One of the candidate co-factors is the β-catenin protein, a pivotal component of the Wnt/β-catenin signaling pathway. β-Catenin mainly implicates two major cellular activities: cell-cell adhesion and signal transduction. Recent studies have indicated that an imbalance in the structural and signaling properties of β-catenin leads to various cancers, such as cervical cancer. In this review, we will systematically summarize the role of β-catenin in cervical cancer and provide new insights into therapeutic strategies.

Keywords: Cell–cell adhesion; Cervical cancer; Wnt signaling pathway; β-Catenin.

Fig. 1

The structure of β-catenin. β-Catenin has a central armadillo repeat domain (residues 141-664) composed of 12 armadillo repeats, flanked by well-defined amino terminus domain (NTD) and carboxyl terminus domain (CTD)

Fig. 2

E-Cadherin/β-catenin complex. This complex is a crucial element in cell–cell adhesion; it consists of three proteins: E-cadherin, β-catenin, and α-catenin. E-Cadherin immobilizes newly synthesized β-catenin to the cell membrane and α-catenin links β-catenin to the actin cytoskeleton

Fig. 3

Wnt/β-catenin signaling pathway. In the absence of the Wnt signal, free cytoplasmic β-catenin is recognized and recruited by the destruction complex, where CK1 and GSK3β phosphorylate it, thereby undergoes ubiquitination-dependent proteolysis. In the presence of Wnt ligands, Wnt signaling blocks the activity of the destruction complex, and subsequently, β-catenin accumulate. Increased levels of cytoplasmic β-catenin translocate into the nucleus, where it associates with DNA binding proteins from the TCF/LEF family and other co-transcription factors. β-Catenin-TCF/LEF transcription complex then drives the transcription of Wnt/β-catenin target genes