Abstract 4411: Cadherin engagement induces a dramatic increase in tyr-705 phosphorylation of the signal transducer and activator of transcription-3 (Stat3α) but not the dominant-negative isoform Stat3β
Notice bibliographique
Résumé
Abstract The purpose of this study was to examine the role of Stat3α and Stat3β in survival and apoptosis of normal and tumor cells. The Stat3 transcription factor is activated by cytokine receptors of the IL6 family, and receptor and non-receptor tyrosine kinases, plays an etiological role in neoplasia. Stat3 activation entails phosphorylation at tyr-705, Stat3 dimerization through a reciprocal, SH2 domain-phosphotyrosine interaction, and nuclear translocation. This triggers transcription of genes involved primarily in cellular survival such as survivin, MCl1 and Bcl-xL, as well as cell division such as myc. We previously demonstrated that engagement of E- or N-cadherin or cadherin-11 induces a dramatic increase in total protein levels and activity of the small GTPases, Rac and Cdc42, through inhibition of proteasomal degradation. Activated Rac leads to a surge in secretion of cytokines of the IL6 family through the transcription factor NFκB and Jak kinases, and this in turn, activates Stat3 in an autocrine manner. Stat3 inhibition in confluent, non-transformed cells induces apoptosis, pointing to a key survival role for Stat3. Full-length Stat3 (termed Stat3α) is composed of an SH2 domain, tyr-705 and a COOH terminus encoding the transcription activation domain (TAD). Stat3β is a naturally-occurring splice variant which is lacking TAD. Therefore, Stat3β dimerizes with Stat3α but is defective in transcriptional activation, resulting in inhibition of Stat3α function. Since tyr-705 is present in both isoforms, we examined the phosphorylation pattern of Stat3α vs Stat3β. Our results demonstrate that cadherin engagement brought about through confluence of non-transformed mouse fibroblasts results in phosphorylation of Stat3α-tyr705, despite the fact that the sequence around tyr-705 is the same in both isoforms. The Large Tumor antigen of Simian virus 40 oncogene (TAg) interacts with the p53 and pRb tumor-suppressors, and this leads to activation of the E2F family of transcription factors, targeting cell division genes. At the same time E2F is a potent apoptosis inducer, hence the high demand of transformed cells for antiapoptotic signals, such as Stat3. Interestingly, our data demonstrated that SVLT expression results in phosphorylation of Stat3β. Therefore, this feedback loop that reduces the activity of Stat3α, triggers apoptosis of transformed cells selectively, because of their high E2F levels. As a result, certain tumor cells which may naturally express high Stat3β levels would be very sensitive to pharmacological Stat3 inhibition, a finding which could have significant therapeutic implications. Citation Format: Zaid Taha, Stephanie Guy, Maximillian Niit, Leda Raptis, Adina Vultur, Rozanne Arulanandam. Cadherin engagement induces a dramatic increase in tyr-705 phosphorylation of the signal transducer and activator of transcription-3 (Stat3α) but not the dominant-negative isoform Stat3β. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4411.
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 | 0,001 | 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) | 0,001 | 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 ».