Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer
Abstract The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin‐driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin f...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202302229 |
| _version_ | 1797637388518817792 |
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| author | Yerbol Tagay Sina Kheirabadi Zaman Ataie Rakesh K. Singh Olivia Prince Ashley Nguyen Alexander S. Zhovmer Xuefei Ma Amir Sheikhi Denis Tsygankov Erdem D. Tabdanov |
| author_facet | Yerbol Tagay Sina Kheirabadi Zaman Ataie Rakesh K. Singh Olivia Prince Ashley Nguyen Alexander S. Zhovmer Xuefei Ma Amir Sheikhi Denis Tsygankov Erdem D. Tabdanov |
| author_sort | Yerbol Tagay |
| collection | DOAJ |
| description | Abstract The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin‐driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein‐generated forces is identified. These forces arise within a non‐stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein‐powered locomotion becomes indispensable during invasive 3D migration within a tissue‐like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis. |
| first_indexed | 2024-03-11T12:47:41Z |
| format | Article |
| id | doaj.art-6c4b370f3bd44940bf2f77028aaf781a |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T12:47:41Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-6c4b370f3bd44940bf2f77028aaf781a2023-11-04T08:56:52ZengWileyAdvanced Science2198-38442023-11-011031n/an/a10.1002/advs.202302229Dynein‐Powered Cell Locomotion Guides Metastasis of Breast CancerYerbol Tagay0Sina Kheirabadi1Zaman Ataie2Rakesh K. Singh3Olivia Prince4Ashley Nguyen5Alexander S. Zhovmer6Xuefei Ma7Amir Sheikhi8Denis Tsygankov9Erdem D. Tabdanov10Department of Pharmacology Penn State College of Medicine The Pennsylvania State University Hershey PA 17033 USADepartment of Chemical Engineering The Pennsylvania State University University Park PA 16802 USADepartment of Chemical Engineering The Pennsylvania State University University Park PA 16802 USADepartment of Obstetrics & Gynecology Gynecology Oncology University of Rochester Medical Center Rochester NY 14642 USACenter for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD 20903 USACenter for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD 20903 USACenter for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD 20903 USACenter for Biologics Evaluation and Research U.S. Food and Drug Administration Silver Spring MD 20903 USADepartment of Chemical Engineering The Pennsylvania State University University Park PA 16802 USAWallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USADepartment of Pharmacology Penn State College of Medicine The Pennsylvania State University Hershey PA 17033 USAAbstract The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin‐driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein‐generated forces is identified. These forces arise within a non‐stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein‐powered locomotion becomes indispensable during invasive 3D migration within a tissue‐like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.https://doi.org/10.1002/advs.202302229contact guidancedyneingranular hydrogelmechanobiologymicrotubulesmotility |
| spellingShingle | Yerbol Tagay Sina Kheirabadi Zaman Ataie Rakesh K. Singh Olivia Prince Ashley Nguyen Alexander S. Zhovmer Xuefei Ma Amir Sheikhi Denis Tsygankov Erdem D. Tabdanov Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer Advanced Science contact guidance dynein granular hydrogel mechanobiology microtubules motility |
| title | Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer |
| title_full | Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer |
| title_fullStr | Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer |
| title_full_unstemmed | Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer |
| title_short | Dynein‐Powered Cell Locomotion Guides Metastasis of Breast Cancer |
| title_sort | dynein powered cell locomotion guides metastasis of breast cancer |
| topic | contact guidance dynein granular hydrogel mechanobiology microtubules motility |
| url | https://doi.org/10.1002/advs.202302229 |
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