-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma
Notice bibliographique
Résumé
BACKGROUND: The role of β-catenin in cancer has been most studied in tumors of epithelial cell origin. The functional status and biological significance of this protein in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is unknown. DESIGN AND METHODS: ALK-positive anaplastic large cell lymphoma cell lines and patients' tumor samples were examined for status of β-catenin expression and signaling. The subcellular localization of β-catenin was assessed using immunohistochemistry, sub-cellular fractionation and confocal microscopy, while its transcriptional activity was studied using the TOPFlash/FOPFlash luciferase reporter assay. To examine the biological significance of β-catenin, short interfering RNA was used to knock-down its expression; the resulting biological effects were studied using trypan-blue exclusion and MTS assay, and the impact on its various downstream targets was assessed using quantitative real-time polymerase chain reaction and western blots. RESULTS: β-catenin was transcriptionally active in three of three ALK-positive anaplastic large cell lymphoma cell lines, and this finding correlates with the nuclear localization of β-catenin in these cells and the neoplastic cells identified in most of the patients' tumor samples. β-catenin is biologically significant in ALK-positive anaplastic large cell lymphoma, since down-regulation of β-catenin resulted in a significant reduction in their cell growth. Down-regulation of β-catenin led to a marked reduction in both the total protein level and the activated/phosphorylated form of STAT3, another signaling protein previously shown to be important in the pathogenesis of ALK-positive anaplastic large cell lymphoma. In contrast to some of the oncogenic tyrosine kinases, modulation of nucleophosmin-anaplastic lymphoma kinase expression did not result in any detectable change in the protein level, nuclear localization or tyrosine phosphorylation of β-catenin; however, inhibition of nucleophosmin-anaplastic lymphoma kinase expression significantly down-regulated the transcriptional activity of β-catenin. CONCLUSIONS: β-catenin signaling is constitutively active in ALK-positive anaplastic large cell lymphoma and represents a previously unknown mechanism by which the high levels of STAT3 expression and activation in these tumors are sustained. Our results suggest that the interaction between oncogenic tyrosine kinases and various cell signaling proteins may be more complex than previously believed.
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 ».