The reduced expression of e-cadherin, alpha-catenin and gamma-catenin but not beta-catenin in human lung cancer.

Toyoyama, Hironobu; Nuruki, Kensuke; Ogawa, Hiroki; Yanagi, Masakazu; Matsumoto, Hajime; Nishijima, Hironobu; Shimotakahara, T; Aikou, Takashi; Ozawa, Masayuki

doi:10.3892/or.6.1.81

Cited by 14 publications

(14 citation statements)

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“…While this appears to be a rather rare event in lung cancers, we show in the present study that reduced or negligible expression of g-catenin is a relatively frequent occurrence in cultured NSCLC cells as well as in *30% of primary lung tumors (Figures 1 and 3). Our findings in this regard are consistent with other studies noting reduced expression of g-catenin in primary lung tumors (Pantel et al, 1998;Pirinen et al, 2001;Toyoyama et al, 1999). In preliminary studies, we have found that reduced tumor expression of g-catenin correlates with poorer tumor differentiation and increased lymph node metastasis and is significantly associated with reduced patient survival (Bremnes RM and Franklin WA, submitted).…”

Section: Discussionsupporting

confidence: 92%

γ-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth

et al. 2002

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Section: Discussionsupporting

confidence: 92%

γ-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth

et al. 2002

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“…The suppression of E-cadherin expression has been reported to be a frequent event in multiple solid tumor types (33) including NSCLC (12)(13)(14)(15)(16). Whether mesenchymal-like cells are retained within tumors and whether they can be detected and measured distinctly from infiltrating stromal cells remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…It has become increasingly clear over recent years that EMT, already established as a critical developmental process, plays a major role in the progression of cancer (10,11). The loss of E-cadherin has been associated with poor clinical outcome in NSCLC (12)(13)(14)(15)(16). The transition to a mesenchymal phenotype, mediated via transcriptional reprogramming by factors such as Twist (17,18) and Snail (19,20), increases the migratory potential of cancer cells and leads to metastasis.…”

Section: Introductionmentioning

confidence: 99%

Epithelial to Mesenchymal Transition Is a Determinant of Sensitivity of Non–Small-Cell Lung Carcinoma Cell Lines and Xenografts to Epidermal Growth Factor Receptor Inhibition

Thomson¹,

Buck²,

Petti³

et al. 2005

Cancer Research

586

490

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Treatment of second-and third-line patients with non-smallcell lung carcinoma (NSCLC) with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib significantly increased survival relative to placebo. Whereas patient tumors with EGFR mutations have shown responses to EGFR inhibitors, an exclusive role for mutations in patient survival benefit from EGFR inhibition is unclear. Here we show that wild-type EGFR-containing human NSCLC lines grown both in culture and as xenografts show a range of sensitivities to EGFR inhibition dependent on the degree to which they have undergone an epithelial to mesenchymal transition (EMT). NSCLC lines which express the epithelial cell junction protein E-cadherin showed greater sensitivity to EGFR inhibition in vitro and in xenografts. In contrast, NSCLC lines having undergone EMT, expressing vimentin and/or fibronectin, were insensitive to the growth inhibitory effects of EGFR kinase inhibition in vitro and in xenografts. The differential sensitivity of NSCLC cells with epithelial or mesenchymal phenotypes to EGFR inhibition did not correlate with cell cycle status in vitro or with xenograft growth rates in vivo, or with total EGFR protein levels. Cells sensitive to EGFR inhibition, with an epithelial cell phenotype, did exhibit increased phosphorylation of EGFR and ErbB3 and a marked increase in total ErbB3. The loss of E-cadherin and deregulation of B-catenin associated with EMT have been shown to correlate with poor prognosis in multiple solid tumor types. These data suggest that EMT may be a general biological switch rendering non-small cell lung tumors sensitive or insensitive to EGFR inhibition. (Cancer Res 2005; 65(20): 9455-62)

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“…They include cell growth and differentiation, cell recognition and sorting during developmental morphogenesis (reviewed in Ref. 2), and a role in certain pathological processes, including the correlation between loss of E-cadherins at the level of cell surface and enhanced cell invasiveness in vitro (6 -9) and tumor progression in vivo (10,11).…”

mentioning

confidence: 99%

Activation of the Protein Kinase Akt/PKB by the Formation of E-cadherin-mediated Cell-Cell Junctions

Pece

Chiariello

Murga

et al. 1999

Journal of Biological Chemistry

241

113

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E-cadherins are surface adhesion molecules localized at the level of adherens junctions, which play a major role in cell adhesiveness by mediating calcium-dependent homophylic interactions at sites of cell-cell contacts. Recently, E-cadherins have been also implicated in a number of biological processes, including cell growth and differentiation, cell recognition, and sorting during developmental morphogenesis, as well as in aggregationdependent cell survival. As phosphatidylinositol (PI) 3-kinase and Akt play a critical role in survival pathways in response to both growth factors and extracellular stimuli, these observations prompted us to explore whether E-cadherins could affect intracellular molecules regulating the activity of the PI 3-kinase/Akt signaling cascade. Using Madin-Darby canine kidney cells as a model system, we show here that engagement of E-cadherins in homophylic calcium-dependent cell-cell interactions results in a rapid PI 3-kinase-dependent activation of Akt and the subsequent translocation of Akt to the nucleus. Moreover, we demonstrate that the activation of PI 3-kinase in response to cell-cell contact formation involves the phosphorylation of PI 3-kinase in tyrosine residues, and the concomitant recruitment of PI 3-kinase to E-cadherin-containing protein complexes. These findings indicate that E-cadherins can initiate outside-in signal transducing pathways that regulate the activity of PI 3-kinase and Akt, thus providing a novel molecular mechanism whereby the interaction among neighboring cells and their adhesion status may ultimately control the fate of epithelial cells.The maintenance of structural and functional integrity of epithelia requires highly dynamic cell-to-cell and cell-to-matrix interactions, which are mediated by adhesion mechanisms involving different types of cell-surface receptors. Among them, cadherins and integrins play a major role, as they are able to recognize and interact with other cell adhesion receptors on neighboring cells or with proteins of the extracellular matrix, respectively (1-3). E-cadherins belong to the family of integral membrane glycoproteins promoting homophylic calciumdependent cell-cell interactions and are well characterized adhesion receptors found within adherens-type junctions in epithelia. The extracellular domain of E-cadherins is able to mediate per se calcium-dependent homotypic interactions at sites of cell-cell contacts, while its highly conserved intracytoplasmic tail is involved in the strengthening of the homophylic adhesions by binding a set of related proteins called catenins which, in turn, link the complex to the actin cytoskeleton and elicit certain nuclear responses (4, 5). Recently, the dynamic aspects of cell adhesion and its relationship to physiological and pathophysiological events have been intensively investigated. They include cell growth and differentiation, cell recognition and sorting during developmental morphogenesis (reviewed in Ref.2), and a role in certain pathological processes, including the correlation betw...

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The reduced expression of e-cadherin, alpha-catenin and gamma-catenin but not beta-catenin in human lung cancer.

Cited by 14 publications

References 0 publications

γ-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth

γ-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth

Epithelial to Mesenchymal Transition Is a Determinant of Sensitivity of Non–Small-Cell Lung Carcinoma Cell Lines and Xenografts to Epidermal Growth Factor Receptor Inhibition

Activation of the Protein Kinase Akt/PKB by the Formation of E-cadherin-mediated Cell-Cell Junctions

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