Glycogen synthase kinase 3β (GSK3β) regulates numerous signaling pathways that control a wide range of cellular processes, including cell proliferation, differentiation, apoptosis and metabolism. We report a novel function of GSK3β: It interacts with the inhibitor-of-apoptosis protein (IAP) survivin to modulate its expression, thus regulating apoptosis in human lung cancer cells. A coimmunoprecipitation assay revealed that GSK3β can bind survivin. Activation of GSK3β induced translocation of survivin from the cytoplasm to the nucleus, resulting in G1 cell-cycle arrest and apoptosis, as well as sensitization to the chemotherapeutic drug doxorubicin. In contrast, inactivation of GSK3β, either by transfection of a dominant-negative mutant inhibitor DN-GSK3β or with selective inhibitor LiCl, increased cytoplasmic survivin expression, leading to cell cycle progression and resistance to apoptosis. These results identify a pro-apoptotic role for GSK3β in cancer cells, through its modulation of survivin in subcellular redistribution. This new role suggests that there is a potential for pharmacologic activation of GSK3β to enhance treatment of cancer patients, including those with resistance.

Aim of the study is to evaluate the expression of CK19, galectin-3, HBME-1, CD56,claudin-1andneutrophilgelatinase-associatedlipocalin(NGAL)inpapillarythyroidcarcinoma(PTC),includingclassic,follicularvariantandmicro-carcinoma.Peritumoralbenignthyroidtissueswereusedasacontrol(C). ImmunohistochemicalstainingwiththeEnVisiondetectionsystemwasperformedon 59formalin-fixed,paraffin-embeddedthyroidtissues,including43PTCand16C. CK19, galectin-3, HBME-1, claudin-1 and NGAL were positive in most PTC, butwerenegativeorshowedfocalweakstaininginC.CD56waspositiveinC,but ab sentinPTC.Forasingleanalyzedtumormarker,thesensitivityoftheabovesix thyroidtumormarkerswas100%,95.3%,86%,79.1%,90.7%,93%,respectively.Thespecificitywas56.25%,100%,100%,100%,100%,100%,respectively. Forthecombinationofthesixtumormarkers,thesensitivity,specificity,positive predictive value, negative predictive value and the diagnostic accuracy were all 100%,withco-expressionofatleastfourindices. InthediagnosisofPTC,combinedapplicationoftheabovetumormarkersisrecommended.ItcanbediagnosedasPTCclearlywhenthyroidlesionsarepositivefor atleastfouroftheabovetumormarkers[CD56(-)],andcanbeexcludedasPTC definitelywhenatleastfourtumormarkersarenegative[CD56(+)].

No abstract

Cigarette smoke exposure is a major cause of chronic obstructive pulmonary disease (COPD), but the underlying molecular inflammatory mechanisms remain poorly understood. Previous studies have found that smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the adherens junction proteins, primarily E-cadherin (E-cad) and p120-catenin (p120). Recently, the anti-inflammatory role of p120 has drawn increasing attention. In this study, we demonstrate that p120 has a role in the cigarette smoke extract-induced inflammatory response, presumably by regulating NF-κB signaling activation. Mechanistically, we show that p120-mediated NF-κB signaling activation in airway epithelial inflammation is partially RhoA dependent and is independent of E-cad. These results provide novel evidence for the role of p120 in the anti-inflammatory response.