Beyond cytoskeletal dynamics: Actin‑binding proteins as multifaceted regulators in tumour progression and therapy (Review)

Actin-binding proteins (ABPs) have long been recognized as core modulators that control actin filament assembly and disassembly inside eukaryotic cells.Scientific focus has heavily centered on cytoskeleton remodelling associated with tumour cell migration, while overlooking the non-structural regulatory effects of ABPs across oncogenic signalling, epigenetic transcription and drug response.The dual functional phenotypes of classical ABPs, including cofilin, profilin, α-actinin and drebrin, across diverse malignant tumours have been comprehensively investigated, further examining how post-translational modification and subcellular localization switch their oncogenic or tumour-suppressive effects.Notably, the present review highlighted non-canonical ABP signalling crosstalk with the Hippo, Ras homologous (Rho) guanosine triphosphatase (GTPase) and phoshoinositide 3-kinase (PI3K)/protein kinase B (Akt) axes and stratified all ABP-targeted interventions by preclinical maturity: Small-molecule compounds, monoclonal antibodies, RNA interference and clustered regularly short palindromic repeats (CRISPR) gene editing.Unresolved translational barriers, including poor target selectivity, intracellular delivery obstacles and protein functional redundancy were also summarized.Current evidence indicated that ABPs cannot be simply defined as pro-tumour or anti-tumour factors; their biological output strictly depends on tumour subtype, disease stage and the intracellular microenvironment.Addressing the druggability defects of ABP family proteins may provide novel opportunities for developing metastasis-specific anti-cancer therapeutic regimens.Further mechanistic validation of ABP-centred signalling networks will facilitate the future development of isoform-selective anti-metastatic therapeutic strategies for clinical oncology.Contents 1. Introduction 2. Literature search strategy 3. Physiological functions of ABPs 4. Pathophysiological significance in tumour progression 5. Regulation of ABPs 6. Clinical therapeutic targets 7. Future directions and challenges 8.