Vimentin-mediated buffering of internal integrin β1 pool increases survival of cells from anoikis.

Autor: Jang J; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea., Park HJ; Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Republic of Korea., Seong W; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea., Kim J; Donnelly Centre, University of Toronto, ON, Toronto, M5S 3E1, Canada., Kim C; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea. chungho@korea.ac.kr.
Jazyk: angličtina
Zdroj: BMC biology [BMC Biol] 2024 Jun 24; Vol. 22 (1), pp. 139. Date of Electronic Publication: 2024 Jun 24.
DOI: 10.1186/s12915-024-01942-w
Abstrakt: Background: The intermediate filament protein vimentin is widely recognized as a molecular marker of epithelial-to-mesenchymal transition. Although vimentin expression is strongly associated with cancer metastatic potential, the exact role of vimentin in cancer metastasis and the underlying mechanism of its pro-metastatic functions remain unclear.
Results: This study revealed that vimentin can enhance integrin β1 surface expression and induce integrin-dependent clustering of cells, shielding them against anoikis cell death. The increased integrin β1 surface expression in suspended cells was caused by vimentin-mediated protection of the internal integrin β1 pool against lysosomal degradation. Additionally, cell detachment was found to induce vimentin Ser38 phosphorylation, allowing the translocation of internal integrin β1 to the plasma membrane. Furthermore, the use of an inhibitor of p21-activated kinase PAK1, one of the kinases responsible for vimentin Ser38 phosphorylation, significantly reduced cancer metastasis in animal models.
Conclusions: These findings suggest that vimentin can act as an integrin buffer, storing internalized integrin β1 and releasing it when needed. Overall, this study provides insights regarding the strong correlation between vimentin expression and cancer metastasis and a basis for blocking metastasis using this novel therapeutic mechanism.
(© 2024. The Author(s).)
Databáze: MEDLINE
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