Monocyte chemoattractant protein-1(MCP-1)is a chemotactic cytokine that can bind to its receptor cysteine-cysteine chemokine receptor 2(CCR2)and plays an important role in breast cancer cell metastasis.However,the molecular mechanisms underlying MCP-1-induced alterations in cellular functions during tumor progression are poorly understood.Here,we showed that MCP-1 stimulated the epithelial-mesenchymal transition(EMT)and induced the tumorigenesis of breast cancer cells by downregulating E-cadherin,upregulating vimentin and fibronectin,activating matrix metallopeptidase-2(MMP-2),and promoting migration and invasion.Moreover,MCP-1 treatment reduced glycogen synthase kinase-3β(GSK-3β)activity via the MEK/ERK-mediated phosphorylation of serine-9 in MCF-7 cells.The inhibition of MEK/ERK by U0126 attenuated the MCP-1-induced phosphorylation of GSK-3βand decreased the expression of Snail,an EMT-related transcription factor,leading to the inhibition of MCF-7 cell migration and invasion.Inactivation of GSK-3βby LiCl(lithium chloride)treatment notably increased MMP-2 activity,vascular endothelial growth factor expression and EMT of MCF-7 cells.These findings revealed that MCP-1-induced EMT and migration are mediated by the ERK/GSK-3β/Snail pathway,and identified a potential novel target for therapeutic intervention in breast cancer.
This work is a supplement to the work of Sneddon on axisymmetric Boussinesq problem in 1965 in which the distributions of interior-stress fields are derived here for a punch with general profile.A novel set of mathematical procedures is introduced to process the basic elastic solutions(obtained by the method of Hankel transform,which was pioneered by Sneddon)and the solution of the dual integral equations.These processes then enable us to not only derive the general relationship of indentation depth D and total load P that acts on the punch but also explicitly obtain the general analytical expressions of the stress fields beneath the surface of an isotropic elastic half-space.The usually known cases of punch profiles are reconsidered according to the general formulas derived in this study,and the deduced results are verified by comparing them with the classical results.Finally,these general formulas are also applied to evaluate the von Mises stresses for several new punch profiles.
Introduction Hematogenous metastasis is the mainly leading cause of death in breast carcinoma patients.A better understanding of the underlying molecular and cellular mechanisms is crucial for the development of effective treatment for metastatic breast cancer[1].It has been well established that cell adhesion and invasion is mediated by a variety of transmembrane proteins,including integrins,cadherins,selectins,and intercellular adhesion molecules.Among these adhesion molecules,the integrins and their downstream signaling pathways have been extensively studied[2].On the other hand,the specific events determining tumor cell interactions with endo-
Fenglong ZhaoLi LiLiuyuan GuangHong YangChunhui WuYiyao Liu
