Notch-1 Signaling Induced Suspension Breast Cell Adhesion Is Mediated By Microtentacles Information

Metastasis pose the primary challenge in clinical management of breast cancer disease.The tumor undergoes angiogenesis during metastasis,providing a pathway for tumor escape and must successfully attach to endothelial cells and extravasate into the parenchyma of foreign tissues after entering the circulatory system.When the tumor is in the circulatory system,it forms a dynamic microtubule-based structure,importantly,invasive breast tumor cells produce more and more pronounced McTNs than noninvasive cell lines.MsTNs promote homotypic aggregation of cells and promote cell reattachment to the extracellular matrix,endothelial monolayer.The formation of McTNs depends on stable microtubules in vivo,and the stability of the microtubule network is also associated with migration control,highlighting potential therapeutic targets for adherent and suspended diffuse cells.The formation of McTNs is dependent on stable microtubules in vivo,and the stability of the microtubule network is also associated with migration control,highlighting potential therapeutic targets for adherent and suspended diffuse cells.The formation of McTNs is dependent on stable microtubules in vivo,and the stability of the microtubule network is associated with migration control,highlighting potential therapeutic targets for adherent and suspended diffuse cells.Meanwhile,the activation of Notch signaling pathway is closely associated with the development of malignant behaviors such as tumor cell growth,adhesion,and migratory invasion,and this paper demonstrates that Notch-1 activation induce McTNs formation to increase suspension cancer cell reattachment.In this study,using confocal fluorescence microscope,we for the first time demonstrated that activated Notch-1 pathway could induce the production of McTNs in MDA-MB-231 cells and increased suspension culture tumor cells re-attachment.Immunoimprinting experiment and immunofluorescence test found that the activation of Notch-1 decreased HDA6 to increase ?-tubulin acetylation level and stable microtubule organization.in order to verify these results,we transfection ?-tubulin acetylation and acetylation-resistant of mutants,found that acetylation microtubules can promote Notch-1 shRNA cell produce more McTNs,both length and number of cells were significantly higher than that of the untransfected cells.The adhesion of cells in the acetylated mutant was significantly higher than that of the untransfected cells.On the other hand,when we transfection MRLC-AA to reduce the cell contraction force,found MRLC-AA group cells compared with MRLC-WT and MRLC-DD cells increased McTNs structure,we once again by Western Blot to verify the activation of Notch-1 decreased MRLC phosphorylation level.In summary,these results clarified that the formation of McTN is mediated in the reattachment of breast cancer cells induced by Notch-1 signaling pathway,providing a new research target and direction for the mechanism of breast cancer metastasis.