Fig. 8

Role of the hydrodynamic shear stress (+SS) in the conversion of epithelial tumor cells into cancer stem-like cells (CSLCs)/tumor-initiating cells (TICs). Proliferating tumor cells near the periphery of solid tumor mass are translocated into nearby blood vessels due to the nature of loose mosaic vessels. Once translocated into blood vessels, epithelial tumor cells are constantly exposed to severe SS in the systemic circulation and prone to dying in the absence of a strong survival signal. +SS given to tumor cells generate reactive free radial species, reactive oxygen species (ROS) and nitric oxide (NO), and cause transcriptional changes in ROS-dependent and NO-dependent pathways along with multiple SS-associated gene pathways. These early signaling events lead to active suppression of extracellular signal-related protein kinase (ERK) and glycogen synthase kinase (GSK)3β pathways to confer plasticity on the epithelial tumor cells, and maintain undifferentiated mesenchymal stem cell properties. As a result, tumor cells acquire survival benefit within the blood circulation with elevated stemness, Epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET) properties, invasive properties, and multi-drug resistance phenotype. CT-PCs, breast cancer cells derived from chemotherapy-treated patients