Vimentin-mediated Buffering of Internal Integrin β1 Pool Increases Survival of Cells from Anoikis

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2024 Jun 24

PMID 38915055

Authors

JiYoung Jang

Hyun Jung Park

Wonyoung Seong

Jiyoon Kim

Chungho Kim

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells.

Rosier M, Krstulovic A, Kim H, Kaur N, Enakireru E, Symmes D Cancers (Basel). 2025; 17(1.

PMID: 39796712 PMC: 11720119. DOI: 10.3390/cancers17010081.

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