Glycogen synthase kinase-3 beta regulates Snail and β-catenin expression during Fas-induced epithelial–mesenchymal transition in gastrointestinal cancer

Zheng, Haoxuan; Li, Wenjing; Wang, Yadong; Liu, Zhizhong; Cai, Yidong; Xie, Tingting; Shi, Meng; Wang, Zhiqing; Jiang, Bo

doi:10.1016/j.ejca.2013.03.014

Cited by 67 publications

(75 citation statements)

References 39 publications

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“…18 The expression of CD95 on cancer cells suggests that cancer cells maintain CD95 expression for activities other than apoptosis induction. Consistent with this assumption are data demonstrating roles for CD95 in promoting cancer cell migration, growth, epithelial-to-mesenchymal transition (EMT), and development, as shown in lung cancer, 19,20 colon cancer, [21][22][23][24] gastrointestinal cancers, 25,26 pancreatic cancer, 27,28 glioblastoma multiforme (GBM), 29 and in 22 cell lines representing various cancers. 30 Our most recent finding is that cancer fails to develop in mouse models of low-grade or endometrioid ovarian cancer or liver cancer unless CD95 is expressed, 14,31 suggesting that the reason cancer cells usually express CD95 goes beyond a function of CD95 as a tumor promoter.…”

Section: Nonapoptotic Signaling Through Cd95 In Normal Cells and In Csupporting

confidence: 50%

Dice

Marynen

2014

Cell Cycle

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Section: Nonapoptotic Signaling Through Cd95 In Normal Cells and In Csupporting

confidence: 50%

Dice

Marynen

2014

Cell Cycle

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“…Inactivation of GSK-3b increases the accumulation of Snail protein levels without affecting transcription (25) and therefore, using Western blot analysis, we examined the levels of phospho-GSK-3b (inactive form) in RV-infected cells. Compared with sham, RV infection increased GSK-3b phosphorylation on Ser 9 significantly at 7 days postinfection, which preceded increased abundance of Snail protein ( Figures 5E and 5F).…”

Section: Rv Enhances Expression Ofmentioning

confidence: 99%

Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

Faris¹,

Ganesan²,

Chattoraj³

et al. 2016

Am J Respir Cell Mol Biol

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Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia.Keywords: barrier function; epithelial-to-mesenchymal transition; Crumbs polarity complex; epithelial growth factor receptor; goblet cell hyperplasia Clinical RelevanceTo the best of our knowledge, this is the first study to demonstrate that rhinovirus delays cell repolarization in a model of injured/regenerating, but not normal, airway epithelium by inducing epithelial-to-mesenchymal transition-like features. Furthermore, rhinovirus reduces ciliated cell differentiation and promotes goblet-cell differentiation and mucin gene expression. These changes depended partially on persistent EGFR activation induced by rhinovirus. Such changes during regeneration can lead to airway epithelium with impaired barrier and mucociliary clearance functions.Airway epithelium that lines the respiratory tract acts as a physical barrier between the external environment and the lung and plays an important role in maintaining tissue homeostasis. Paracellular permeability of airway epithelium is maintained through the co-operation of two functionally distinct structural components: tight and adherence junctions located in the apicolateral membranes. Tight junctions regulate the transport of solutes and ions across airway epithelium...

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“…Snail is a zinc-finger transcription factor that may promote EMT, and overexpression of Snail is associated with lymph node metastasis and a poor prognosis in patients with GC (10,11). In GC, NF-κB activation by tumor necrosis factor-Z, cyclooxygenase-2 and Rho guanosine diphosphate-dissociation inhibitor 2 increase Snail expression, and Snail downregulates E-cadherin and promotes EMT (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…Snail then downregulates E-cadherin expression and promotes EMT. Finally, the activation of EMT leads to tumor metastasis (12)(13)(14)24). Analysis of the prognosis of patients with combined CXCL1 and Snail expression, the CXCL1 + /Snail + group exhibited a worse prognosis compared with the other groups, particularly the CXCL1 -/Snail -group.…”

mentioning

confidence: 99%