Shear stress promotes anoikis resistance of cancer cells via caveolin-1-dependent extrinsic and intrinsic apoptotic pathways

Journal of Cellular Physiology
Shun LiYiyao Liu

Abstract

Circulating tumor cells (CTCs) need to acquire resistance to anoikis to survive after they experience fluid shear stress in the circulatory and lymphatic systems. However, the mechanism by which tumor cells resist anoikis under shear stress conditions remains unknown. Here, we found that the application of low shear stress (LSS; 2 dyn/cm2 ) to human breast carcinoma cells (MDA-MB-231) resulted in increased anoikis resistance when tumor cells were grown under anchorage-independent conditions. Caveolin-1 (Cav-1), the major component of plasma membrane caveolae, was overexpressed in LSS-treated cells and prevented tumor cells from anoikis, while depletion of Cav-1 restored sensitivity to anoikis. LSS-induced dissociation of Cav-1-Fas inhibited formation of the death-inducing signaling complex, caspase-8 activation, and rendered tumor cells resistant to anoikis. Likewise, LSS blocked the mitochondrial pathway through promotion of integrin β1-focal adhesion kinase-mediated multicellular aggregation and suppression of truncated BID translocation mediated crosstalk between the extrinsic and intrinsic apoptotic pathways. Our findings provide insights into the mechanisms by which LSS induces anoikis resistance in breast carcinoma cells ...Continue Reading

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Citations

Feb 6, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Carlyne D CoolNorbert F Voelkel
Aug 1, 2019·Biomolecules·America CamposAndrew Frederick Geoffery Quest
Jul 28, 2020·International Journal of Molecular Sciences·Han-A ParkYonghyun Kim
Dec 1, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Xiang QinYiyao Liu
Mar 2, 2021·Frontiers in Bioengineering and Biotechnology·Sebastian E Amos, Yu Suk Choi
Jul 3, 2021·International Journal of Molecular Sciences·Joana Godinho-PereiraMaria Alexandra Brito

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