Cortactin Dynamics in Cell Migration and Actin Polymerization

Cortactin is an actin‐binding protein that orchestrates the assembly and branching of filamentous actin networks. By engaging the Arp2/3 complex and other nucleation factors, cortactin promotes the formation of lamellipodia and invadopodia—specialised protrusions that drive cell motility and matrix invasion. Its activity is modulated by post-translational modifications, including tyrosine phosphorylation, serine phosphorylation and acetylation, which govern its interactions with kinases, adhesion complexes and signalling partners. Through these regulatory cycles, cortactin integrates external cues such as growth factors, chemokines and mechanical tension to direct cytoskeletal reorganisation. In endothelial and epithelial barriers, cortactin sustains junctional integrity, whereas in immune cells it underpins chemotaxis and synapse formation. Aberrant expression or modification of cortactin is a hallmark of invasive cancers and inflammatory disorders, making it a promising target for therapeutic intervention in metastasis, vascular leak and immune dysregulation.

Research from Nature Portfolio

Recent studies have shown that preparations of human amniotic membrane homogenate and extract downregulate cortactin and key regulators of actin reorganisation in muscle-invasive bladder cancer cells. This reduction in cortactin expression correlates with diminished focal adhesion kinase (FAK) activity, decreased epithelial–mesenchymal transition markers and impaired cell migration, suggesting new avenues for anticancer therapies based on modulation of cytoskeletal dynamics.

Foundational work on endothelial physiology revealed that loss of cortactin leads to heightened actomyosin contractility via upregulation of ROCK1 and reduced secretion of the barrier-stabilising hormone adrenomedullin. Restoration of adrenomedullin levels or pharmacological ROCK1 inhibition reverses barrier disruption, highlighting cortactin’s critical role in vascular permeability and offering insight into treatments for inflammatory oedema.

Cortactin Dynamics in Cell Migration and Actin Polymerization publication trend

The graph below shows the total number of articles in cortactin dynamics in cell migration and actin polymerization across all publications each year (not limited to Nature Index journals).

Technical terms

Cortactin: An actin-binding protein that recruits and activates the Arp2/3 complex to promote filament branching and lamellipodial extension.

Arp2/3 complex: A seven-subunit protein assembly that initiates new actin filaments from the sides of existing filaments, generating a branched network.

Actin polymerization: The process by which globular actin monomers assemble into filamentous actin (F-actin), driving changes in cell shape and motility.

Lamellipodia: Broad, sheet-like membrane protrusions at the leading edge of migrating cells, formed by dense networks of branched actin filaments.

Invadopodia: Actin-rich protrusions specialised for extracellular matrix degradation, facilitating invasive behaviour of cancer cells.

Focal adhesion: Multiprotein complexes that link the extracellular matrix to the actin cytoskeleton, transmitting mechanical and biochemical signals.

References

1. Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation. iScience (2023).
2. Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway. Scientific Reports (2023).
3. Effects of Cortactin Expression on Prognosis in Patients with Breast Cancer. Diagnostics (2023).
4. Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility. Scientific Reports (2016).
5. Cortactin Overexpression Regulates Actin-Related Protein 2/3 Complex Activity, Motility, and Invasion in Carcinomas with Chromosome 11q13 Amplification. Cancer Research (2006).