Role of ACTB in Breast Cancer EMT and Metastatic Progression: An Integrated Multi-Omics and Network-Based Study

Abstract

Beta-actin (ACTB), a major cytoskeletal protein, plays a crucial role in the epithelial-to-mesenchymal transition (EMT) that facilitates breast cancer metastasis. By driving actin cytoskeletal remodelling, ACTB enables cancer cells to acquire migratory and invasive phenotypes. This study integrates multi-omics data, pathway and protein interaction analyses, and genetic evidence to characterise ACTB's role in breast cancer progression. The findings highlight ACTB’s pivotal function as a network hub orchestrating cell motility and invasion via regulation of cytoskeletal dynamics and signalling pathways such as TGF-β, Wnt/β-catenin, and Rho GTPases. While direct therapeutic targeting of ACTB is limited by its ubiquitous essentiality, associated actin-binding proteins, post-translational modifications, and metabolic dependencies emerge as promising intervention points. ACTB and its modifications also show potential as prognostic biomarkers for aggressive breast cancer subtypes. This comprehensive profiling advances understanding of ACTB’s pathogenic role and guides future anti-metastatic therapy development.