73 253

Cited 95 times in

Claudin-1 induces epithelial-mesenchymal transition through activation of the c-Abl-ERK signaling pathway in human liver cells.

Authors
Suh, Y; Yoon, CH; Kim, RK; Lim, EJ; Oh, YS; Hwang, SG; An, S; Yoon, G; Gye, MC; Yi, JM; Kim, MJ; Lee, SJ
Citation
Oncogene, 32(41):4873-4882, 2013
Journal Title
Oncogene
ISSN
0950-92321476-5594
Abstract
Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, β-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.
MeSH terms
Carcinoma, Hepatocellular/metabolism/pathologyCell Line, TumorClaudin-1/*metabolism*Epithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP Kinases/*metabolismGene Expression Regulation, NeoplasticHomeodomain Proteins/metabolismHumansLiver/metabolism/*pathologyLiver Neoplasms/metabolism/*pathologyNeoplasm InvasivenessProto-Oncogene Proteins c-abl/*metabolismProto-Oncogene Proteins c-raf/metabolism*Signal TransductionTight Junctions/metabolismTranscription Factors/metabolismras Proteins/metabolism
DOI
10.1038/onc.2012.505
PMID
23160379
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
윤, 계순
Files in This Item:
fulltext not available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse