Abstract 2307: Cellular expression of E-cadherin but not its plasma membrane localization is regulated by the PTEN/PI 3 Kinase pathway via transcription factors twist and snail
Notice bibliographique
Résumé
Abstract Introduction: 90% of carcinoma-related deaths in adults and children are associated with cancer metastasis. Metastasis involves phenotypical changes in cancer cells within the primary tumor. To acquire motility and invasiveness, carcinoma cells must shed many epithelial phenotypes, detach from neighboring cells and undergo a series of drastic alterations commonly referred to as the “Epithelial-Mesenchymal Transition (EMT)”. In normal epithelium, E-cadherin expression provides high-affinity anchoring to neighboring cells, serving as a tumor suppressor mechanism. With malignant transformation, N-cadherin is upregulated. Results: Using a panel of cell lines representing the various stages of melanoma progression, [primary melanocytes (HEMA-LP); radial (WM 35); vertical (WM793) and metastatic (A2058) growth phases], we have confirmed a switch in cadherin phenotype from E- to N-cadherin. The greatest expression of E-cadherin is evident in the HEMA-LP cell line, with null expression in A2058. N-cadherin is expressed abundantly in WM793 and A2058, with almost null expression in Hema-LP. Interestingly, there is also a loss of expression of the tumor suppressor PTEN in WM793 and A2058. Transfection of wild type PTEN in A2058 cells resulted in re-expression of E-cadherin and a drop in N-cadherin levels. We also determined that the PTEN-modulated switch in cadherin profile is regulated at the transcriptional level, and involves the transcription factors Twist and Snail. Cellular expression of Twist and Snail was greatest in A2058 cells and lowest in HEMA-LP cells. Transfection of PTEN into A2058 cells caused a decrease in expression of Twist and Snail. Further, targeted knockout of Twist with shRNA in A2058 cells resulted in suppression of N-cadherin expression and the appearance of E-cadherin, while transfection of a Twist over-expression vector in HEMA-LP resulted in suppression of E-cadherin expression and the appearance of N-cadherin. Surprisingly, the invasive capacity of the A2058 cells was only reduced by 40% in the presence of PTEN. Immunofluorecent analysis of E-cadherin expression in A2058 cells indicated that this may be due to the fact that the re-expressed E-cadherin does not become targeted and localized to the plasma membrane. Conclusion: We define a pathway that regulates cellular E- & N-cadherin expression modulated at the transcriptional level by the PTEN/PI-3 Kinase pathway and involves the transcription factors twist and snail. However, the targeted localization of E-cadherin to the plasma membrane is not regulated by this pathway but by other mechanism(s) that have not yet been identified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2307.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».