Abstract 993: A novel cadherin-dependent Rac/Stat3 pathway in invasive breast cancer
Notice bibliographique
Résumé
Abstract Stat (signal transducer and activator of transcription) 3 is a transcription factor involved in a number of signaling pathways activated by receptor and non-receptor tyrosine kinases. Constitutively active Stat3 alone is sufficient to induce tumorigenesis. We have previously shown that Stat3 can also be activated by engagement of the epithelial adhesion molecule E-cadherin (MCR 7:1310-27, 2009). An additional novel finding in this study was that levels of total and activated Rac1 proteins increase dramatically, thereby causing the Stat3 stimulation. Interestingly, Stat3 expression was independently found to downregulate p53 expression in several epithelial and fibroblast cell lines. These findings suggest a novel Cadherin/Rac1/Stat3-dependent pathway that causes sustained downregulation of p53, resulting in uncontrolled growth and survival. As a first step to test this hypothesis in breast cancer, we are assessing the expression profiles and localization of these molecules in mouse breast epithelial and carcinoma cell lines. The results revealed that at low cell density in 2-D culture conditions, E-cadherins and b-catenin showed strong cytoplasmic and perinuclear localization, respectively. In contrast, at high cell density both markers showed strong localization to the plasma membrane. On the other hand, a breast carcinoma cell line showed cytoplasmic staining of pan-cadherin and nuclear staining of β-catenin under both low and high cell density conditions. Western blotting revealed that levels of pan and activated (pY705) Stat3, and Rac1 were increased at high compared to low cell densities, consistent with a cadherin-dependent activation of this pathway. We are currently extrapolating these findings to a 3-D Matrigel culture model in which mammary epithelial cells (EPH4) form acini-like spheroids with hollow. Under these conditions, total Stat3 levels are sustained for 4-6 days followed by a transient increase in cyclin D1 expression. We are also performing immunohistochemical analyses of these molecular biomarkers on a cohort of human breast cancer tissues (n=59) to test associations of protein expression profiles in human cancer. Preliminary results have shown increased expression of active Stat3 in breast tumours compared to normal mammoplasty tissues. In addition, increased expression of p53 was observed in a subset (17%) of these breast cancers. Detailed ARIOL imaging analysis is currently in progress to evaluate relative expression levels and associations of Stat3 and p53 in breast cancer tissues. Our findings suggest a novel pathway by which Stat3 activation causes a dramatic decrease in p53 levels, resulting in increased proliferation and survival of cancer cells. (Supported by CIHR and CBCRA). 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 993.
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 | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».