TI - E-cadherin/beta-catenin/T - cell factor pathway is involved in smooth muscle cell proliferation elicited by oxidized low-density lipoprotein . AB - The E-cadherin/beta-catenin/T-cell factor ( Tcf ) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis . The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density lipoprotein ( LDL ) . In human aortic smooth muscle cells , mitogenic concentration of mildly oxidized LDL induced the activation of beta-catenin , as assessed by the dissociation of the beta-catenin/cadherin complex , and the concomitant rise of active beta-catenin in the cytosol . The oxidized LDL -induced rise of active beta-catenin required metalloproteinase activation , as well as epidermal growth factor receptor and Src signaling , as assessed by the use of pharmacological inhibitors and cells overexpressing a SrcK-inactive form . The concomitant phosphatidylinositol 3-kinase/Akt activation and glycogen synthase kinase 3-beta phosphorylation induced the inhibition of the proteasomal degradation of beta-catenin . Then active beta-catenin associated with Tcf4 and translocated into the nucleus . This enhanced the expression of the cell cycle activator cyclin D1 . This crucial role of beta-catenin in the mitogenic effect of oxidized LDL was confirmed by silencing beta-catenin by specific small interfering RNA that blocked DNA synthesis . Immunohistochemistry staining of stable and disrupted plaques from carotid endarterectomy sections showed a correlation between active beta-catenin and Ki67 , a proliferation marker , and a more intense staining in the smooth muscle cell layer surrounding the lipid core of disrupted plaques . In conclusion , the beta-catenin pathway is required for the mitogenic effect of oxidized LDL on human aortic smooth muscle cells . This study highlights the putative important role of the E-cadherin/beta-catenin/Tcf signaling pathway in atherosclerosis .