Shear stress regulates the migration of suspended breast cancer cells by nuclear lamina protein A/C and large tumor suppressor through yes-associated protein.

Abstract

Breast cancer is life threatening among women because its migration by hematogenous metastasis, where, besides biochemical cues, breast circulating tumor cells (CTCs) expose to suspension state and shear stress. However, the combined effects of these mechanical factors on CTCs migration were unclear. Here, suspension state and shear stress were loaded to breast tumor cells (BTCs) to mimic two mechanical cues in the mechanical environment of breast CTCs and the mechanobiological mechanism of suspension state and shear stress regulating the migration of (BTCs) was investigated. The migration and nuclear lamina protein A/C (Lamin A/C) accumulation were enhanced in MDA-MB-231 and SK-BR-3 BTCs exposed to shear stress though lower than that of suspended cells with different yes-associated protein (YAP) subcellular localization. Knockdown of LMNA downregulated and upregulated YAP targets in suspended BTCs and BTCs exposed to shear stress, respectively, which inhibited MDA-MB-231 BTCs migration in vitro and in vivo. Large tumor suppressor (LATS) responded to suspension state and shear stress, knockdown of which decreased the migration of MDA-MB-231 BTCs. These findings uncover the mechanobiological mechanism that suspension state and shear stress antagonistically promote BTCs migration by Lamin A/C and LATS through YAP and the potential for targeting YAP in CTCs prognosis. Shear stress regulates suspended breast cancer cells migration by Lamin A/C and LATS through YAP.