The E-cadherin/Catenin Complex in Invasion and Metastasis

Bracke, Marc; Roy, Frans van; Mareel, Marc

doi:10.1007/978-3-642-61107-0_9

Cited by 155 publications

(114 citation statements)

References 274 publications

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“…Rat intestinal epithelial cells treated with TGF-b1 and EGF show a decrease of E-cadherin, a common characteristic of almost all human epithelial cancers (Bracke et al, 1996). Our data show that TGF-b1 and EGF-induced EMT is initiated before substantial loss of E-cadherin in RIE cells.…”

Section: Discussionmentioning

confidence: 57%

Synergistic effect between EGF and TGF-β1 in inducing oncogenic properties of intestinal epithelial cells

et al. 2007

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Transforming growth factor (TGF)-b1 has a biphasic effect on rat intestinal epithelial (RIE) cells. By itself, TGF-b1 functions as a tumor suppressor by inhibiting the growth, migration and invasion of RIE cells. We show in this study that in conjunction with epidermal growth factor (EGF), TGF-b1 helped to augment migration, invasion and anchorage-independent growth (AIG) compared to that by EGF alone. EGF plus TGF-b1 induced a dramatic morphological change characteristic of epithelial-mesenchymal transition (EMT). The mechanism for this enhanced effect of TGF-b1 and EGF on oncogenic properties was explored by analysis of EGF-and TGF-b1-mediated signaling pathways and complementary DNA arrays. TGF-b1 augmented EGF-mediated signaling of mitogen-activated protein kinase (MAPK) and AKT by enhancing and prolonging the activation of the former and prolonging the activation of the latter. Inhibition of MAPK, but not phosphoinositide-3 kinase (PI3K), abolished TGF-b1 plus EGF-induced EMT and downregulation of E-cadherin at mRNA and protein levels. By contrast, cell migration and invasion were sensitive to inhibition of either MAPK or PI3 kinase. TGF-b1 plus EGF-induced AIG was significantly more resistant to inhibition of PI3K and MAPK compared to that induced by EGF alone. EGF and TGF-b1 synergistically induced the expression of a series of proteases including matrix metalloproteinase (MMP) 1 (collagenase), MMP3, MMP9, MMP10, MMP14 and cathepsin. Among them, the expression of MMP1, MMP3, MMP9 and MMP10 was MAPK dependent. Inhibition of the MMPs or cathepsin significantly blocked EGF plus TGF-b1-induced invasion, but had no effect on colony formation.Phospholipase C (PLC) and Cox2 induced by EGF plus TGF-b1 also played a significant role in invasion, whereas PLC was also important for colony formation. Our study reveals specific signaling functions and induction of genes differentially required for enhanced effect of EGF-and TGF-b1-induced oncogenic properties, and helps to explain the tumor-promoting effect of TGF-b1 in human cancer with elevated expression or activation of TGF-b1 and receptor protein tyrosine kinases.

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Section: Discussionmentioning

confidence: 57%

Synergistic effect between EGF and TGF-β1 in inducing oncogenic properties of intestinal epithelial cells

et al. 2007

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“…However, the molecular mechanisms of hepatocarcinogenesis and intrahepatic metastasis are not yet well understood (Bergsland and Venook, 2000). Loss of both cell-cell adhesion and cellular differentiation is one of the characteristics of malignant cells, and this has been reported extensively to correlate with E-cad down-regulation (Bracke et al, 1996;Endo et al, 2000;Huang et al, 1999;Takeichi, 1993). Reduced E-cad expression due to transcriptional repressor Snail around CDH1 promoter region may participate in certain steps of carcinogenesis by reduction of intercellular adhesiveness, which may result in initiation of invasion and destruction of normal tissue morphology (Batlle et al, 2000;Cano et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Abnormalities in expression and cellular distribution of E-cad are frequently associated with dedifferentiation, invasiveness, and lymph node or distance metastasis in a variety of human malignancies including primary HCC (Bracke et al, 1996;Endo et al, 2000;Takeichi, 1993). E-cad is also a critical factor in the process of intrahepatic metastasis of HCC (Osada et al, 1996).…”

mentioning

confidence: 99%

Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo

2002

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Hepatocellular carcinoma is a well-known malignancy in the world. However, the molecular mechanism of carcinogenesis and tumour progression remains unclear. Recently, reduced E-cadherin expression due to transcriptional suppressor Snail was proven in a panel of epithelial and dedifferentiated cells derived from carcinomas of various etiologies. In the present study, we examined Snail and E-cadherin mRNA/protein expression in five hepatocellular carcinoma cell lines with variable phenotypes (HuL-1, Hep-G 2 , Changliver, HLE, and HLF). The results demonstrated that the presence of Snail mRNA in HuL-1, Changliver, HLE and HLF cells detected by RT -PCR, which was further proven by in situ hybridization in tumours induced by HuL-1, Changliver, and HLF cells where Snail mRNA signals expressed in each of the sections. By contrast, E-cadherin mRNA and protein expression were only detected in Hep-G 2 cells by RT -PCR and Western blot, respectively. These results were also consistent with the data obtained from in vivo immunohistochemical staining where membranous expression of endogenous Ecadherin protein was revealed only in tumour sections induced by Hep-G 2 cells. Here we are the first to report that there is an inverse correlation between Snail and E-cadherin expression in HCC cells as well.

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“…15 The cell-cell adhesion molecule, E-cadherin, linked by its cytoplasmic part via ␤-catenin or plakoglobin and ␣-catenin to the actin cytoskeleton, acts as an invasion suppressor. 16 The E-cadherin/catenin complex is often disturbed in cancer cells at various levels, namely by mutations in the cadherin or catenin genes, reduced stability of mRNAs, tyrosine phosphorylation of ␤-catenin, intra-and extracellular associations with other proteins, steric hindrance of enlarged proteoglycans and by ectodomain shedding of histidine alanine valine (HAV)-containing E-cadherin-specific peptides. Inactivation of the E-cadherin/catenin complex leads to increased invasiveness as documented in experimental as well as clinical cancers.…”

Section: -O-octadecyl-2-o-methyl-glycerophosphocholine (Et-18-ome)mentioning

confidence: 99%

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

et al. 2001

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1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18 Key words: alkyl-lysophospholipid; E-cadherin; episialin; adhesion; invasion1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OMe) interacts with cell membranes, thereby modulating phospholipid metabolism, interfering with signal transduction, inducing apoptosis and differentiation and regulating invasion. 1 On solid substrate, the E-cadherin/catenin complex is implicated in the cell-cell adhesion of 2 variants of the MCF-7 human breast cancer cell line family, coined MCF-7/AZ and MCF-7/6. In suspension, however, MCF-7/6 cells are adhesion-deficient while MCF-7/AZ cells are adhesion-proficient. Treatment with ET-18-OMe caused antithetic effects on the 2 types of MCF-7 cells. ET-18-OMe restored the E-cadherin function in the adhesiondeficient MCF-7/6 cells, whereas it caused a decrease in cellular aggregation of the adhesion-proficient MCF-7/AZ cells. The latter effects could not be explained by changes in sialylation of Ecadherin. 2 Antithetic effects on invasion have also been reported: ET-18-OMe inhibited invasion of constitutively invasive cells, [3][4][5][6] whereas it induced invasion of otherwise noninvasive cells. 7,8 Inhibition of invasion in the presence of ET-18-OMe was explained by induction of host tissue resistance, 9 but the antithetic effects on cell-cell adhesion and the invasion-promoting effect of ET-18-OMe have not been explained.Adhesion and invasion are the result of a balance between promoter and suppressor molecules modulated by multiple intraand extracellular factors. The presence of the anti-adhesion molecule episialin on the 2 types of MCF-7 cells was observed in a previous study. 2 The aim of our study was to see whether ET-18-OMe affects invasion and adhesion through modulation of episialin and E-cadherin.Episialin is a heterodimeric molecule composed of a membrane anchor and an extracellular moiety. The membrane anchor consists of a cytoplasmatic domain of 68 amino acids and a transmembrane domain. The extracellular moiety consists of a large mucin domain containing a large number of O-linked glycans. 10 The carbohydrate side chains carry many sialic acid residues conveying a highly negative charge upon episialin. 11 Episialin is located at the apical surface of most glandular epithelial cells; it is over-expressed in carcinomas, often distributed over the entire cell surface. 11 Overexpression of episialin inhibits integrin-mediated cell adhesion to

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The E-cadherin/Catenin Complex in Invasion and Metastasis

Cited by 155 publications

References 274 publications

Synergistic effect between EGF and TGF-β1 in inducing oncogenic properties of intestinal epithelial cells

Synergistic effect between EGF and TGF-β1 in inducing oncogenic properties of intestinal epithelial cells

Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

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