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  • Hypotaurine br Materials and methods br Results br Discussio

    2022-05-20


    Materials and methods
    Results
    Discussion Cell migration not only plays major roles in physiological events, such as embryo implantation, embryogenesis, morphogenesis, neurogenesis, angiogenesis, wound healing and inflammation [[29], [30], [31]], but it is also implicated in the pathophysiology of many diseases such as cancer. Indeed, metastatic behaviour, which varies widely between cancers, defines the malignancy of tumours, and metastasis is one of the main causes of cancer-related mortality [32]; additionally, metastases are usually comprised of Hypotaurine that are much more resistant, aggressive and efficient than those forming the primary tumour [33]. Some studies have reported that mechanical or chemical stimulation consistently affects the ability of cells to migrate [34,35]. Interestingly, in our study, we found that low-level shear stress significantly promoted LCSC migration. This finding suggested that shear stress may regulate the migration of LCSCs. Moreover, the FAK-ERK1/2 signalling pathway was activated in LCSCs after exposure to shear stress. PF573228 and PD98059 inhibited the shear stress-induced phosphorylation of FAK and ERK1/2, and blocked shear stress-induced LCSC migration, which for the first time demonstrated a relationship between the FAK-ERK1/2 signalling pathway and shear stress-induced LCSC migration. Several in vitro studies have demonstrated that phosphorylation of FAK correlates with an increase in cell migration [36,37]. FAK directly activates downstream effectors such as ERK1/2, and it has been shown that upregulation of FAK phosphorylation promotes cell migration through ERK1/2 [38]. In our study, we found that shear stress appears to promote LCSC migration by activating the phosphorylation of FAK and ERK1/2. These results will help us to better understand how shear stress influences LCSC migration. Cell mechanics have become crucial elements in research on cell migration. In combination with biochemical assays, such studies provide the opportunity to probe the complex behaviour of a single motile cell in a more comprehensive manner than previously possible. The cytoskeletal network has been hypothesized to play a major role in determining the mechanical properties of living cells. It has been postulated that spatiotemporal regulation of the mechanical behaviours of the filamentous actin (F-actin) cytoskeleton network may regulate cellular shape and force generation during cell migration [39]. In this study, we found that LCSCs stimulated with shear stress for 6 h formed less F-actin than control cells, as evidenced by the staining of F-actin with TRITC-conjugated phalloidin. Recently, several studies have revealed a strong relationship between F-actin and metastatic potential. In our previous study, we also found that LCSCs enriched from MHCC97H cells exhibit a higher metastatic potential and significant lower F-actin content than non-enriched MHCC97H cells [2]. Babahosseini et al. demonstrated that the formation of F-actin leads to a decrease in the migration capability of ovarian cancer cells [34], which is consistent with the findings of our study. In this study, we also found that LCSCs stimulated with shear stress for 6 h formed less F-actin than control cells, and the FAK-ERK1/2 signalling pathway plays a pivotal role in this process. FAK is a primary signalling mediator of dynamic actin cytoskeletal reorganization, and FAK activation is necessary for tubulin stabilization [35]. Kobayashi et al. demonstrated that FAK signalling is the initiation point of a signalling cascade through which osteoprotegerin induces cytoskeletal reorganization, microtubule elongation, and cell spreading in HuDMECs [36]. Our previous study also determined that salinomycin attenuates LCSC motility by enhancing cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signalling pathway [40]. In the present study, we discovered a direct correlation between the FAK-ERK1/2 signalling pathway and the cytoskeleton in shear stress-induced LCSC migration.