Background:Myosin X (MYO10) was recently reported to promote tumour invasion by transporting integrins to filopodial tips in breast cancer. However, the role of MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required in invadopodia to mediate invasive growth and extracellular matrix degradation, which depends on the binding of MYO10's pleckstrin homology domain to PtdIns(3,4,5)P3.Methods:The expression of MYO10 and its associations with clinicopathological and biological factors were examined in breast cancer cells and breast cancer specimens (n=120). Cell migration and invasion were investigated after the silencing of MYO10. The ability of cells to form invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin degradation assay. A mouse model was established to study tumour invasive growth and metastasis in vivo.Results:Elevated MYO10 levels were correlated with oestrogen receptor status, progesterone receptor status, poor differentiation, and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion. Invadopodia were responsible for MYO10's role in promoting invasion. Furthermore, decreased invasive growth and lung metastasis were observed in the MYO10-silenced nude mouse model.Conclusions:Our findings suggest that elevated MYO10 expression increases the aggressiveness of breast cancer; this effect is dependent on the involvement of MYO10 in invadopodial formation.
This paper proposes a method for computing the removal of material as the abrasive tool follows a path on a three-dimensional surface. The method assumes that the pressure distribution is Hertzian at the contact between the tool and the surface and that the abrading rate follows the Archard wear law. The focus is on the effect of the path curvature on the profile of material removal. Simulation examples are included to illustrate the proposed method. Results indicate that the material removal profile is affected by the geodesic radius of curvature of the tool path. When the radius is large, the profile is almost parabolic. As the radius is reduced, the location of maximum material removal is shifted towards the centre of the geodesic curvature. Moreover, the location can be at the bound of the profile for very small values of the radius.
This paper establishes the dynamic equations of the spatial rigid-flexible coupling multibody systems for a five-coordinate virtual-axis hybrid polishing machine tool, namely model JDYP51 developed by the authors. The dynamic characteristics of the hybrid machine tool are studied in detail by means of the theory of dynamics of a flexible multibody system and the finite element models of the whole machine tool and each leg respectively. The dynamic simulation of the machine shows that the elastic deformation of each leg is very small during the movement of the machine and the influence of the flexibility of each leg on the trace of moving platform is not obvious due to the characteristics of joints. At the beginning of the movement of the machine, the fundamental frequency of parallel mechanism easily leads to vibration of the machine. Therefore, the stable status of polishing can be obtained at all periods of the movement of the machine except the beginning of the movement.
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