Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer

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. He...

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Published inAdvanced science Vol. 10; no. 31; p. e2302229
Main Authors Tagay, Yerbol, Kheirabadi, Sina, Ataie, Zaman, Singh, Rakesh K, Prince, Olivia, Nguyen, Ashley, Zhovmer, Alexander S, Ma, Xuefei, Sheikhi, Amir, Tsygankov, Denis, Tabdanov, Erdem D
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.11.2023
John Wiley and Sons Inc
Wiley
Subjects
Actomyosin - metabolism
Breast cancer
Breast Neoplasms
Cell adhesion & migration
Cell division
Cell Movement
Collagen
Conformity
contact guidance
dynein
Dyneins - metabolism
Female
Genomics
granular hydrogel
Humans
Hydrogels
mechanobiology
Metastasis
microtubules
Motility
dynein
mechanobiology
granular hydrogel
motility
contact guidance
microtubules
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Summary: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.
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ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202302229