Actin Dynamics in Epithelial-Mesenchymal Transition

The process of epithelial-mesenchymal transition (EMT) underpins critical events in embryonic development, tissue repair and cancer metastasis by enabling epithelial cells to shed intercellular adhesion, reorganise their cytoskeleton and acquire motility. Central to this phenotypic switch is the dynamic remodelling of actin networks, which orchestrates changes in cell shape, polarity and adhesion. In epithelial cells, a cortical actin belt reinforces stable adherens junctions; onset of EMT triggers disassembly of these bundles, localised polymerisation into protrusive lamellipodia and filopodia, and reorganisation of stress fibres that drive migration. This rapid turnover is governed by a cohort of actin-binding proteins that promote filament nucleation, elongation, capping and severing in response to extracellular cues such as growth factors, mechanical stiffness and matrix interactions. Rho family GTPases integrate these signals to regulate actomyosin contractility and coordinate adhesion dynamics. Dysregulation of actin dynamics contributes to pathological conditions by facilitating invasive behaviour in carcinoma cells, thereby representing a focal point for therapeutic intervention.

Research from Nature Portfolio

Recent studies have re-evaluated the role of epithelial protein lost in neoplasm (EPLIN) in tumour progression. Unexpectedly, elevated expression of EPLIN in pancreatic cancer has been shown to promote cell migration, survival and resistance to chemotherapeutic agents. Mechanistically, EPLIN modulates MAPK and PI3K-AKT signalling cascades and influences the activity of key EMT transcription factors, thereby enhancing actin filament remodelling and enabling mesenchymal phenotypes under drug stress. Inhibition of EPLIN reverses these effects, restoring epithelial characteristics and sensitising cells to targeted therapies.

Building on foundational insights into mechanical regulation of cytoskeletal architecture, work in migrating cells has demonstrated that extracellular matrix stiffness and actomyosin contractility activate a RhoA-mDia1 pathway to generate detyrosinated microtubule networks. Although conducted in fibroblasts, these findings illuminate how mechanical inputs can be transduced into cytoskeletal realignment, promoting directional actin polymerisation and subcellular RNA localisation that parallel events observed during EMT.

Actin Dynamics in Epithelial-Mesenchymal Transition publication trend

The graph below shows the total number of articles in actin dynamics in epithelial-mesenchymal transition across all publications each year (not limited to Nature Index journals).

Technical terms

Actin polymerisation: Process by which globular actin monomers assemble into filamentous structures driving cytoskeletal remodelling.

Epithelial-Mesenchymal Transition (EMT): Cellular process whereby epithelial cells lose adhesion and polarity to adopt a motile mesenchymal phenotype.

Adherens junctions: Cadherin-based cell–cell adhesion complexes linked to the actin cytoskeleton that maintain tissue integrity.

Actomyosin contractility: Generation of mechanical force through interactions between actin filaments and myosin II motors.

RhoA signalling: Pathway involving the small GTPase RhoA that orchestrates actin organisation and contractile activity.

EPLIN: Actin-binding protein that stabilises filaments and regulates junctional integrity, often lost during EMT.

CAPZA1: α1 subunit of the capping protein complex that binds to the fast-growing ends of actin filaments to regulate their assembly.

References

1. EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer. Scientific Reports (2024).
2. Extracellular matrix stiffness and cell contractility control RNA localization to promote cell migration. Nature Communications (2017).
3. Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis. Cancers (2021).
4. Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition. Cells (2020).
5. Epidermal Growth Factor Promotes Protein Degradation of Epithelial Protein Lost in Neoplasm (EPLIN), a Putative Metastasis Suppressor, during Epithelial-mesenchymal Transition*. Journal of Biological Chemistry (2012).
6. CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research (2017).