CDC42EP5/BORG3 modulates SEPT9 to promote actomyosin function, migration, and invasion
Aaron J Farrugia1, Javier Rodríguez2, Jose L Orgaz3
1Division of Cancer Biology, The Institute of Cancer Research, London, UK.
The Journal of Cell Biology
|August 17, 2020
Summary
The septin regulator Cdc42EP5 is crucial for melanoma cell migration and invasion. It enhances actomyosin contractility by cross-linking actin filaments, coordinating actin and septin networks for metastasis.
Area of Science:
- Cell Biology
- Cancer Research
- Cytoskeletal Dynamics
Background:
- Fast amoeboid migration is vital for development and cancer metastasis.
- Actomyosin contractility drives migration, but its coordination with other cytoskeletal elements is unclear.
- Septins are emerging cytoskeletal components with poorly understood roles in cell motility.
Purpose of the Study:
- To investigate the role of Cdc42EP5 in melanoma cell migration and invasion.
- To elucidate the molecular mechanisms by which Cdc42EP5 regulates actomyosin contractility and cytoskeletal coordination.
Main Methods:
- Investigated Cdc42EP5 function in melanoma cell invasion assays.
- Analyzed the association of Cdc42EP5 with actin structures.
- Examined the impact of Cdc42EP5 on actomyosin contractility and F-actin cross-linking.
- Assessed the role of SEPT9 in Cdc42EP5-mediated functions.
Main Results:
- Cdc42EP5 is essential for amoeboid melanoma cell invasion in collagen matrices and in vivo metastasis.
- Cdc42EP5 associates with actin, increasing actomyosin contractility and promoting migration.
- Cdc42EP5 mediates SEPT9-dependent F-actin cross-linking, stabilizing contractile actomyosin structures.
- SEPT9 is critical for Cdc42EP5's role in melanoma invasion.
Conclusions:
- Cdc42EP5 is a key regulator of cancer cell motility, coordinating actin and septin networks.
- SEPT9 plays a unique role in facilitating melanoma invasion and metastasis through Cdc42EP5.
- Targeting Cdc42EP5 and SEPT9 may offer therapeutic strategies against melanoma dissemination.
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