The role of E-cadherin expression in non-small cell lung cancer

Lim, Sung Chul; Jang, Il; Kim, Young Chul; Park, Kyung Ok

doi:10.3346/jkms.2000.15.5.501

Cited by 25 publications

(20 citation statements)

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“…Several transcription factors such as Slug, Snail, are normally considered repressors for E-cadherin [36,39,40,41]. In A549 cells, the knockdown of RhoGDI2 significantly decreased the expression of E-cadherin, whereas overexpressing RhoGDI2 increased the expression of E-cadherin (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Down-regulation of E-cadherin, a repressor of metastasis, is considered as the hallmark of EMT in cancer [36,37,38]. Several transcription factors such as Slug, Snail, are normally considered repressors for E-cadherin [36,39,40,41].…”

Section: Resultsmentioning

confidence: 99%

“…Its expression is crucial for establishing and maintaining epithelial tissue structure [46]. Down-regulation of E-cadherin decreases cell adhesion strength and promotes motility, hence it is considered the fundamental hallmark of EMT in cancer [5,6,36,37,38]. It is widely accepted that E-cadherin represses cell invasion and metastasis [5,6,37,38], and its activity can be regulated by several transcription factors e.g., Slug and Snail especially in lung carcinoma [36,39,40,41].…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Huang¹,

Wu²,

Jiang³

et al. 2014

Cell Physiol Biochem

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Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT) process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR), western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Huang¹,

Wu²,

Jiang³

et al. 2014

Cell Physiol Biochem

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“…Unlike resistant cells, NSCLC cell lines that are highly sensitive to EGFR TKIs retain moderate to high levels of E-cadherin (Yauch et al, 2005;Soltermann et al, 2008;Kakihana et al, 2009). Moreover, loss of E-cadherin is associated with poor prognosis and is a major contributor to the early mortalities in NSCLC patients (Lim et al, 2000;Thompson et al, 2005;Yauch et al, 2005;Witta et al, 2006;Frederick et al, 2007;Soltermann et al, 2008). In NSCLC cell lines, E-cadherin expression is modulated through two main signaling pathways, namely b-catenin and zinc finger proteins, including transcriptional repressors Snail, Slug, Zeb1, and SIP1 (Zeb2) (Postigo and Dean, 1999;Ohira et al, 2003;Peinado et al, 2004;Witta et al, 2006;Kakihana et al, 2009;Schmalhofer et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…This is primarily attributed to the early metastatic spread of the disease within the lung and to distant organs, which involves epithelial-tomesenchymal transition (EMT) of lung cancer cells including non-small cell lung cancer (NSCLC) cells (Denlinger et al, 2010). NSCLC cells differ widely in their basal level of E-cadherin, which is an epithelial marker and responsible for the "integrity of the cell" by maintaining cell polarity, cell shape, and cell-cell contact (Lim et al, 2000;Bremnes et al, 2002;Chaffer and Weinberg, 2011). The differential expression of E-cadherin in NSCLC cell lines is due to its epigenetic silencing via deacetylation-and methylation-related events regulated by epigenetic enzymes, e.g., histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) that deacetylate histones and methylate DNA, respectively (Johnstone, 2002;Jones and Baylin, 2002;Belinsky, 2004;Witta et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Silibinin Synergizes with Histone Deacetylase and DNA Methyltransferase Inhibitors in Upregulating E-cadherin Expression Together with Inhibition of Migration and Invasion of Human Non-small Cell Lung Cancer Cells

Mateen

Raina

Agarwal

et al. 2013

J Pharmacol Exp Ther

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Aggressive cancers in the epithelial-to-mesenchymal transition (EMT) phase are characterized by loss of cell adhesion, repression of E-cadherin, and increased cell mobility. Non-small cell lung cancer (NSCLC) differs in basal level of E-cadherin; predominantly exhibiting silenced expression due to epigeneticrelated modifications. Accordingly, effective treatments are needed to modulate these epigenetic events that in turn can positively regulate E-cadherin levels. Herein, we investigated silibinin, a natural flavonolignan with anticancer efficacy against lung cancer, either alone or in combination with epigenetic therapies to modulate E-cadherin expression in a panel of NSCLC cell lines. Silibinin combined with HDAC inhibitor Trichostatin A [TSA; 7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide] or DNMT inhibitor 59-Aza-deoxycytidine (Aza) significantly restored E-cadherin levels in NSCLC cells harboring epigenetically silenced E-cadherin expression. These combination treatments also strongly decreased the invasion/migration of these cells, which further emphasized the biologic significance of E-cadherin restoration. Treatment of NSCLC cells, with basal E-cadherin levels, by silibinin further increased the E-cadherin expression and inhibited their migratory and invasive potential. Additional studies showed that silibinin alone as well as in combination with TSA or Aza downmodulate the expression of Zeb1, which is a major transcriptional repressor of E-cadherin. Overall these findings demonstrate the potential of combinatorial treatments of silibinin with HDAC or DNMT inhibitor to modulate EMT events in NSCLC cell lines, leading to a significant inhibition in their migratory and invasive potentials. These results are highly significant, since loss of E-cadherin and metastatic spread of the disease via EMT is associated with poor prognosis and high mortalities in NSCLC.

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The value of E‐cadherin/ β‐catenin expression in imprints of NCSLC: Relationship with clinicopathological factors

Pagaki

Patsouris²,

Gonidi³

et al. 2010

Diagnostic Cytopathology

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Metastasis is specific for malignant tumors and its control is one of the most important problems in the design of therapies for cancer patients. Loss or reduction of E-cadherin expression and/or beta-catenin expression plays a casual role in tumor progression and metastasis and is associated with poor prognosis. The purpose of the study is to investigate the expression of E-cadherin and beta-catenin and their significance as independent prognostic markers in imprints of resected nonsmall cell lung cancer (NSCLC). Imprint smears from 70 patients who underwent surgical lung resection for primary carcinoma were studied. As control group was used imprints of physiological tissues. Histologically 47 (67.1%) of the tumors were squamous cell carcinomas and 23 (32.9%) were adenocarcinomas. Tumors stage was I in 29 (41.4%), II in 13 (18.6%), III in 24 (34.3%) and IV in 4 (5.7%). Positive expression for E-cadherin was observed in 44.29% of malignant smears vs 85.71% for control group (P = 0.011). For beta-catenin, positive expression was observed in 42.86% malignant cases vs 85.71% for control group (P = 0.008). Positive expression of E-cadherin and beta-catenin was observed in moderate and well differentiated tumors (P < 0.0001 for both respectively). Positive E-cadherin and beta-catenin expression was observed in 70.6% and 76.5% of the cases with negative lymphnode metastasis (P < 0.0001 for both respectively). There was no statistically significant association between histological type, tumor stage, pleural invasion, tumor size (P > 0.05 for all) and E-cadherin/beta-catenin expression.Reduced E-cadherin or beta-catenin negative expression relates to dedifferentiation and progression of NSCLC.

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The role of E-cadherin expression in non-small cell lung cancer

Cited by 25 publications

References 0 publications

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

Silibinin Synergizes with Histone Deacetylase and DNA Methyltransferase Inhibitors in Upregulating E-cadherin Expression Together with Inhibition of Migration and Invasion of Human Non-small Cell Lung Cancer Cells

The value of E‐cadherin/ β‐catenin expression in imprints of NCSLC: Relationship with clinicopathological factors

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