Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia
Abstract Invadopodia, dynamic cancer cell protrusions, deform and degrade extracellular matrix (ECM) to facilitate invasion. Intracellular calcium ions (Ca2+) are critical second messengers involved in cancer cells migration, proliferation, and apoptosis, but their role in invadopodia dynamics remai...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
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| Series: | Communications Physics |
| Online Access: | https://doi.org/10.1038/s42005-025-02268-x |
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| Summary: | Abstract Invadopodia, dynamic cancer cell protrusions, deform and degrade extracellular matrix (ECM) to facilitate invasion. Intracellular calcium ions (Ca2+) are critical second messengers involved in cancer cells migration, proliferation, and apoptosis, but their role in invadopodia dynamics remains unclear. Here, we propose a chemo-mechanical model integrating Ca2+ transmembrane transport, myosin contractility, adhesion dynamics, actin polymerization, and membrane type 1 matrix metalloproteinase (MT1-MMP) hydrolysis. We find that increased invadopodia length elevates membrane tension, activating mechanosensitive channels and raising intracellular Ca2+ levels, aligning with experimental observations. Our model reveals that invadopodia oscillatory and monotonic dynamics are governed by actin polymerization and myosin recruitment, with Ca2+ transport enhancing dynamics via myosin recruitment and reciprocal effects on Ca2+ transport. Furthermore, by incorporating MT1-MMP-mediated ECM degradation in our model, we find that ECM degradation promotes invadopodia extension and elevates Ca2+ levels, which shifts the invadopodia dynamics from monotonic to oscillatory. Overall, our model offers a comprehensive theoretical framework for understanding Ca2+ transport and invadopodia dynamics in cancer cells. |
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| ISSN: | 2399-3650 |