The Role of Beta-Catenin and the Wnt Signalling Pathway in Breast Cancer Initiation, Progression and Metastasis: A Literature Review

Abstract

Introduction: Breast cancer (BC) is a complex disease with significant global health implications and is characterized by heterogeneity in molecular profiles and biomarker expression. The Wnt/β-catenin pathway plays a pivotal role in BC progression, with aberrant Wnt signaling contributing to increased tumorigenicity, metastasis, and therapeutic resistance, particularly in aggressive subtypes, such as triple-negative breast cancer (TNBC) and HER2-negative BC.

Methods: This review synthesizes recent literature on β-catenin and Wnt signaling dysregulation in BC, focusing on the triple-negative and HER2-negative subtypes. Key studies emphasizing molecular mechanisms and therapeutic implications were selected from databases such as PubMed and Google Scholar.

Results: Evidence indicates widespread Wnt/β-catenin pathway dysregulation across multiple breast cancer subtypes. This dysregulation often leads to enhanced proliferation, metastatic potential, and resistance to therapy. In triple-negative disease, nuclear β-catenin accumulation correlates strongly with aggressiveness. Additionally, crosstalk with pathways like PI3K/AKT and HER2 further augments oncogenic behavior.

Discussion: In BC, dysregulation of the Wnt/β-catenin pathway can lead to abnormal β-catenin accumulation and activation of oncogenic genes, contributing to tumor growth, metastasis, and resistance to therapy. The Wnt pathway, which is crucial for normal cellular processes, is frequently dysregulated in BC and contributes to increased tumorigenicity, metastasis, and therapeutic resistance. This review presents findings that demonstrate the intricate interactions between Wnt/ β-catenin signaling and other critical pathways, including PI3K/AKT and HER2, and elucidates how these interactions contribute to the progression of breast cancer. It addresses the impact of genetic mutations on the Wnt/β-catenin signaling pathway in BC, highlighting how these alterations contribute to tumor progression, metastasis, and therapeutic resistance, along with examining the role of its homolog, γ-catenin.

Conclusion: This review includes insights from recent literature on the molecular mechanisms underlying Wnt dysregulation and suggests future research directions to improve therapeutic strategies for BC. By understanding the intricate role of Wnt signaling in BC, we aimed to identify novel targets and develop more effective treatments for this challenging disease.