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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| Format: | Article |
| Language: | English |
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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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| _version_ | 1849226229781102592 |
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| author | Junbo Zhao Haochen Zhang Yuehua Yang Ruihao Xue Ze Gong Hongyuan Jiang |
| author_facet | Junbo Zhao Haochen Zhang Yuehua Yang Ruihao Xue Ze Gong Hongyuan Jiang |
| author_sort | Junbo Zhao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a4dcb86aab7241b2af1737fb3574332f |
| institution | Kabale University |
| issn | 2399-3650 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Physics |
| spelling | doaj-art-a4dcb86aab7241b2af1737fb3574332f2025-08-24T11:33:52ZengNature PortfolioCommunications Physics2399-36502025-08-018111010.1038/s42005-025-02268-xCa2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodiaJunbo Zhao0Haochen Zhang1Yuehua Yang2Ruihao Xue3Ze Gong4Hongyuan Jiang5CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Capital Medical UniversityCAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of ChinaCAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of ChinaCAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of ChinaCAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of ChinaAbstract 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.https://doi.org/10.1038/s42005-025-02268-x |
| spellingShingle | Junbo Zhao Haochen Zhang Yuehua Yang Ruihao Xue Ze Gong Hongyuan Jiang Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia Communications Physics |
| title | Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| title_full | Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| title_fullStr | Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| title_full_unstemmed | Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| title_short | Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| title_sort | ca2 transmembrane transport enhances oscillatory growth of cancer cell invadopodia |
| url | https://doi.org/10.1038/s42005-025-02268-x |
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