Abstract 4004: Reciprocal regulation of Stat3 and the caveolae protein, cav1
Notice bibliographique
Résumé
Abstract Caveolae are cholesterol-rich, flask-shaped invaginations of the plasma membrane with many roles in the cell, including the regulation of signal transduction. Caveolin 1 (Cav1) is the major protein responsible for the organization and maintenance of caveolae microdomains. Cav1 recruits many receptor and non-receptor tyrosine kinases and through binding to its scaffolding-domain, Cav1 sequesters the kinases in an inactive form, thereby preventing their involvement in signaling pathways. One important downstream target of many tyrosine kinases (Src, EGF, PDGF, IL6 and others) is the signal transducer and activator of transcription-3 (Stat3). Stat3 is a cytoplasmic signal transducer which is activated by tyrosine-705 phosphorylation by a number of kinases, then migrates to the nucleus to initiate transcription of genes involved in cell division and survival. Despite extensive evidence on the role of cav1 in signal transduction, its effect upon Stat3 is still obscure. We previously demonstrated that cell-to-cell adhesion, as occurs in confluent cultures, can cause a dramatic increase in Stat3 phosphorylation and activity in cultured cells (Oncogene 23:2600, MBC 16:3832). Therefore, to examine effects upon Stat3, cell density has to be taken into account. Our results now indicate that cav-1 downregulation through expression of an anti-sense construct, or treatment with the pharmacological inhibitor, methyl-cyclo-dextran which removes cholesterol from the membrane and destroys caveolae, caused a strong activation of Stat3 as well as Erk1/2, at all densities examined. Conversely, cav1 overexpression downregulated Stat3 and induced apoptosis in NIH3T3 fibroblasts both before and after transformation by the Simian Virus 40 Large Tumor antigen, as well as in HeLa cells. In all cases, apoptosis was prevented by co-expression of the constitutively active form of Stat3, Stat3C. Taken together, these findings point to cav1 as an inhibitor of Stat3 activity. It was previously demonstrated that cav1 upregulates p53 gene activity. Since Stat3 is known to inhibit p53 transcription by direct binding to the p53 promotor, these data also point to the possibility that cav1 may, in fact, activate p53 through Stat3 inhibition. Our results also demonstrate for the first time that, in a feedback loop, Stat3 inhibition following infection with an Adenovirus vector expressing a Stat3-specific, shRNA, results in a dramatic increase in cav1 levels, indicating that Stat3 also downregulates cav1 expression. Since p53 also upregulates cav1, and Stat3 blocks the p53 promotor, it is possible that Stat3 may block cav1 simply by downregulating p53, rather than downregulating the cav1 promotor directly. The above findings taken together reveal the presence of a potent, negative regulatory loop between cav1 and Stat3 activity that plays a crucial role in cellular survival. (supported by CIHR, CBCF-Ontario chapter, US Army breast cancer program NSERC and BCAK). 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 4004.
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 | 0,001 |
| 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 ».