Disassembly of intercellular junctions is a hallmark of epithelial-mesenchymal transition (EMT). However, how the junctions disassemble remains largely unknown. Here, we report that E3 ubiquitin ligase Smurf1 targets p120-catenin, a core component of adherens junction (AJ) complex, for monoubiquitination during transforming growth factor β (TGFβ)–induced EMT, thereby leading to AJ dissociation. Upon TGFβ treatment, activated extracellular signal–regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. Inhibition of T900 phosphorylation or ubiquitination of p120-catenin abrogates TGFβ-induced AJ dissociation and consequent tight junction (TJ) dissociation and cytoskeleton rearrangement, hence markedly blocking lung metastasis of murine breast cancer. Moreover, the T900 phosphorylation level of p120-catenin is positively correlated with malignancy of human breast cancer. Hence, our study reveals the underlying mechanism by which TGFβ induces dissociation of AJs during EMT and provides a potential strategy to block tumor metastasis.
Nanocrystalline metals developed based on fine grain strengthening always have an excellent strength, but are accompanied by a drop in ductility. In the past 20 years, substantial efforts have been dedicated to design new microstructures and develop the corresponding processing technologies in order to solve this problem. In this article, the novel nanostructures designed for simultaneously achieving high strength and high ductility developed in recent years, including bimodal grain size distribution nanostructure, nanotwinned structure, hierarchical nanotwinned structure, gradient nanostructure, and supra-nano-dual-phase nanostructure, are reviewed. Based on a comprehensive understanding of the simultaneously strengthening and toughening mechanisms, the microstructures and corresponding processing techniques are mainly discussed, and the related prospects that may be emphasized in the future are proposed.
Mg matrix composites reinforced by graphene nanoplatelets (GNPs) offers an efficient approach for improving the mechanical properties of Mg alloys. Unfortunately, the poor uniform dispersion of GNPs into Mg matrix vastly restricts their development. In addition, surface oxidation of Mg alloy powders is always serious. To alleviate these issues, pickling and surface modification technologies of ZK61 Mg alloy powders and mixing process with GNPs have been investigated. The results show that ZK61 alloy powders with smooth surface and low degree of oxidation can be obtained after being simultaneously mechanically stirred and ultrasonically treated for 30 min in a 0.2 vol% HF ethanol solution. They were then rinsed and dried, and modified by 0.3% wt% cetyl trimethyl ammonium bromide to carry a positive charge. Subsequently, GNPs ethanol suspension was poured into the modified ZK61 alloy powders solution and mechanically stirred for 10 min, and then a powder mixture that GNPs randomly attached on the Mg powders was obtained after drying.XPS analysis reveals that GNPs were adsorbed on the surfaces of the modified Mg powders by the mechanism of electrostatic adsorption. The achieved method for preparing GNPs/ZK61 alloy mixture powders provides a new strategy for fabricating Mg matrix composites reinforced by uniformly distributed GNPs.
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