Molecular Mechanisms of ERM Protein Function in Cancer Cell Biology

ERM proteins—ezrin, radixin and moesin—act as pivotal linkers between the plasma membrane and the cortical actin cytoskeleton, orchestrating cell shape, adhesion and motility. In their inactive, closed conformation, the N-terminal FERM domain associates intramolecularly with the C-terminal actin-binding region. Activation entails phosphatidylinositol 4,5-bisphosphate binding and phosphorylation of a conserved threonine residue (for example Thr558 in moesin), which opens the molecule and allows membrane recruitment and actin engagement. Once activated, ERM proteins serve as scaffolds for adhesion receptors, growth-factor signalling complexes and cytoskeletal regulators, thereby modulating the formation of lamellipodia, filopodia and invadopodia. In cancer cells, dysregulation of ERM expression or post-translational modification amplifies oncogenic pathways—such as PI3K/Akt and Rho GTPases—driving enhanced invasion, migration and metastatic potential. Moreover, ERM proteins influence endosomal trafficking and receptor recycling, affecting cell surface presentation of integrins and matrix metalloproteinases that facilitate extracellular matrix remodelling. The emerging global significance of ERM biology in oncology lies in its integrative role in mechanotransduction, signalling crosstalk and cytoskeletal plasticity, offering novel avenues for therapeutic intervention.

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Molecular Mechanisms of ERM Protein Function in Cancer Cell Biology publication trend

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Technical terms

ERM proteins: Ezrin, radixin and moesin, a family of membrane–cytoskeleton crosslinkers that regulate cell shape, adhesion and signalling.

FERM domain: A conserved N-terminal module in ERM proteins that mediates binding to phospholipids and membrane proteins.

Phosphorylation: The covalent attachment of a phosphate group, often triggering conformational changes and activation of target proteins.

Ubiquitination: Post-translational modification in which ubiquitin is attached to a substrate, commonly marking it for proteasomal degradation.

Invadopodia: Actin-rich protrusions that concentrate proteases to degrade extracellular matrix and facilitate invasion.

References

1. FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis. Cell Death & Disease (2023).
2. Intercellular adhesion molecule 2 as a novel prospective tumor suppressor induced by ERG promotes ubiquitination-mediated radixin degradation to inhibit gastric cancer tumorigenicity and metastasis. Journal of Translational Medicine (2023).
3. Cytoskeletal Remodeling in Cancer. Biology (2020).
4. A glimpse of the ERM proteins. Journal of Biomedical Science (2016).
5. Cortical Actin Organization: Lessons from ERM (Ezrin/Radixin/Moesin) Proteins*. Journal of Biological Chemistry (1999).