Epithelial to Mesenchymal Transition of Lung Cancer Cells

Seike, Masahiro; Mizutani, Hideaki; Sudoh, Junko; Gemma, Akihiko

doi:10.1272/jnms.76.181

Cited by 2 publications

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“…This is the first report to show that such, normally fibroblast associated molecular changes occur in purified thymic epithelial cells. In the literature, epithelial-mesenchymal transition is associated with differential expression of E- and N-cadherin [25]. While E-cadherin decreases, N-cadherin normally compensates for the loss of E-cadherin expression.…”

Section: Resultsmentioning

confidence: 99%

Wnt4 and LAP2alpha as Pacemakers of Thymic Epithelial Senescence

et al. 2010

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Age-associated thymic involution has considerable physiological impact by inhibiting de novo T-cell selection. This impaired T-cell production leads to weakened immune responses. Yet the molecular mechanisms of thymic stromal adipose involution are not clear. Age-related alterations also occur in the murine thymus providing an excellent model system. In the present work structural and molecular changes of the murine thymic stroma were investigated during aging. We show that thymic epithelial senescence correlates with significant destruction of epithelial network followed by adipose involution. We also show in purified thymic epithelial cells the age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2α expression. These senescence-related changes of gene expression are strikingly similar to those observed during mesenchymal to pre-adipocyte differentiation of fibroblast cells suggesting similar molecular background in epithelial cells. For molecular level proof-of-principle stable LAP2α and Wnt4-over-expressing thymic epithelial cell lines were established. LAP2α over-expression provoked a surge of PPARγ expression, a transcription factor expressed in pre-adipocytes. In contrast, additional Wnt4 decreased the mRNA level of ADRP, a target gene of PPARγ. Murine embryonic thymic lobes have also been transfected with LAP2α- or Wnt4-encoding lentiviral vectors. As expected LAP2α over-expression increased, while additional Wnt4 secretion suppressed PPARγ expression. Based on these pioneer experiments we propose that decreased Wnt activity and increased LAP2α expression provide the molecular basis during thymic senescence. We suggest that these molecular changes trigger thymic epithelial senescence accompanied by adipose involution. This process may either occur directly where epithelium can trans-differentiate into pre-adipocytes; or indirectly where first epithelial to mesenchymal transition (EMT) occurs followed by subsequent pre-adipocyte differentiation. The latter version fits better with literature data and is supported by the observed histological and molecular level changes.

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Section: Resultsmentioning

confidence: 99%

Wnt4 and LAP2alpha as Pacemakers of Thymic Epithelial Senescence

et al. 2010

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“…According to literature, EMT is associated with differential expression of E-(decrease) and N-cadherin (increase) (Seike et al 2009). TECs were tested for these markers to investigate whether the first step towards pre-adipocyte differentiation is the EMT of epithelial cells.…”

Section: Gene Expression Changes In the Thymic Epithelium During Ageingmentioning

confidence: 99%

Central Immune Senescence, Reversal Potentials

Kvell

Pongrácz

2012

Senescence

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Epithelial to Mesenchymal Transition of Lung Cancer Cells

Cited by 2 publications

References 0 publications

Wnt4 and LAP2alpha as Pacemakers of Thymic Epithelial Senescence

Wnt4 and LAP2alpha as Pacemakers of Thymic Epithelial Senescence

Central Immune Senescence, Reversal Potentials

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