Alteration of the E-Cadherin/beta-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma

BACKGROUND: Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells. METHODS: To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, beta-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival. RESULTS: The loss of E-cadherin expression and aberrant beta-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/beta-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/beta-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314). CONCLUSIONS: The alteration of the expression of the E-cadherin/beta-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.

Role of Keratinocytes in the Development of Vitiligo

Vitiligo is an acquired depigmentary disorder of the skin that results from the loss of functioning epidermal melanocytes. Most studies on vitiligo have concentrated on the abnormality of melanocytes rather than the abnormality of keratinocytes; however, epidermal melanocytes form a functional and structural unit with neighboring keratinocytes. In fact, direct cell-to cell contact stimulates in vitro proliferation of melanocytes, and growth factors produced by adjacent keratinocytes regulate the proliferation and differentiation of melanocytes. The potential role of keratinocyte-derived cytokines has also been presented. We focused on the structural changes in vitiliginous keratinocytes, which may result in loss of melanocytes, to examine the pathomechanism of vitiligo. The results of a comparison between depigmented and normally pigmented epidermis in patients with vitiligo showed that the keratinocytes in the depigmented epidermis were more vulnerable to apoptosis. Impaired Phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt) activation followed by reduced nuclear factor-kappaB activation under increased tumor necrosis factor-alpha levels was demonstrated as a mechanism for keratinocyte apoptosis. The role of aquaporin 3 in keratinocyte apoptosis was addressed based on the relationship between the PI3K/AKT pathway and the E-cadherin-catenin complex. Apoptotic keratinocytes induced a lower expression of keratinocyte-derived factors, including stem cell factor, in depigmented epidermis, resulting in passive melanocyte death.

Effect of gastrin on E-cadherin/?-catenin complex in focal adhesion kinase pathway of CoLo320WT cell lines / 中华消化杂志

Objective To explore the effect of gastrin_(17) on E cadherin/?-catenin complex,a down- stream effector of FAK pathway,in colonic carcinoma cell line CoLo320WT.Methods pCR3.1/GR plasmid expressing gastrin receptor CCK 2R was transfected into colonic carcinoma cell line CoLo320 by Lipofectamine~(TM) 2000 and expressing stably CCK 2R clones was screened by G418.The expression levels of gastrin receptor of Coi.o320 and the transfected cell line Colo320WT were assayed by RT PCR. CoLo320WT cells were treated by 10~(-8)mmol/L gastrin_(17) at distinct time points (0 hr,1 hr,6 hr,12 hr, 24 hr,48 hr),whilst treated by 10_(-6) mmol/L L365,260 (gastrin_(17) receptor blocker) simultaneously for 30 minutes and then treated by gastrin_(17) again for 12 hr.Expression levels of phosphorylated FAK Tyr397 and total FAK in CoLo320WT under gastrin_(17)intervention were detected hy Western blot.Ex- pression levels of E-cadherin and?-catenin complex in TX-100 solution fraction and TX-100 insolution fraction of CoLo320WT cells were detected by coimmunoprecipitation and Western blot.Distribution of E-cadherin and?-catenin in CoLoWT320 were observed by immunocytochemistry.Results Phosphoryla- ted FAK Tyr397 expression in CoLo320WT cells increased in time dependent fashion under gastrin_(17) intervention and peaked at 12 hour after intervention,while decreased by L365,260 inhibition.But gas trine_(17) had no effect on total FAK in CoLo320WT cells.Expresion levels of E-cadherin and?-catenin com- plex in TX-100 solution fraction were decreased apparently,but increased again after L365,260 block- ing.On the contrary,the expression levels of E-cadherin and?-eatenin complex in TX-100 solution frac tion differed from that in TX-100 solution.Cytoehemistry observation had revealed that E-cadherin and?-catenin transferred from cell membranes into cndochylemas,nuclei and cytoskeleton under gastrin_(17) in- tervention.Conclusions Gastrin_(17)affected significantly the distribution of E cadherin/?-catenin complex in CoLo320WT by phosphorating FAK Tyr397 and activating FAK pathway when it bound to its recep- tor CCK-2,therefore promoted invasion and metastasis of CoLo320WT.

Relationship between abnormal expression of E-cadherin-catenin complex in gastric carcinoma and its clinicopathological features as well as patient survival / 中华消化杂志

Objective E cadherin catenin complex mediates cell cell adhesion and plays an important role in maintaining normal architecture and function of epithelial tissues. We evaluated the expression patterns of E cadherin, ? catenin, and ? catenin in gastric carcinoma and determine the potential relationship between E cadherin catenin complex and tumor clinicopathological features as well as patient survival. Methods Immunohistochemical staining of E cadherin, ? catenin, and ? catenin in 148 gastric carcinomas was performed. Results The abnormal expression rates of E cadherin, ? catenin and ? catenin in the tissues of gastric carcinomas were 44.6%, 73.6% and 43.2%, respectively. The total abnormal expression rate of E cadherin complex in 148 cases of gastric carcinoma was 91.9%. Reduced expression of E cadherin, ? catenin and ? catenin were significantly correlated with tumor differentiation status ( P