Abstract 1494: Silencing Notch-1 and Notch-3 promotes epithelial-to-mesenchymal transition (EMT) and self-renewal potential in human bladder cancer.
Notice bibliographique
Résumé
Abstract Background: Beside its regulatory functions during development, the Notch pathway plays an eminent role in the tumorigenesis of malignancies. There are four different Notch receptors, which demonstrate context-dependent activity and can work antagonistically to each other. We have previously described a role for Notch-2 in promoting EMT and invasion in bladder cancer (BCA). Our objective here was to elucidate the role of Notch-1 and -3 in EMT and invasion, hypothesizing that both promote the epithelial, less invasive phenotype. Methods: Immunohistochemistry was performed on a tissue microarray (TMA) of 104 tumors from patients with muscle invasive BCA. Notch-1 and -3 expression was assessed in a panel of bladder cancer cell lines by Western blot (WB) and correlated to previously established EMT status (based on E-cadherin and ZEB1) and invasive ability. Notch-1 and -3 were silenced by lentiviral shRNA vector in 3 cell lines with high constitutive Notch-1 and -3 expression (UM-UC1, UM-UC6 and UM-UC15). Protein and mRNA expression of genes relevant to EMT, invasion and stemness were profiled by WB, real-time PCR, immunofluorescence and FACS. Proliferation, migration and invasion were measured by crystal violet, scratch, and Boyden chamber assays, respectively. Self-renewal potential was assessed by clonogenic assay and spheroid formation in MammoCult™ medium. Results: High expression of Notch-3 receptor was associated with lower pathological stage (p<0.05) and absence of lymphovascular invasion (p<0.05) in the cystectomy specimens. Notch-1 expression did not correlate with pathologic variables. WB revealed expression of Notch-1 and -3 in epithelial bladder cancer cell lines only. Silencing of Notch-1 or Notch-3 in the selected epithelial cell lines promoted EMT at the mRNA and protein levels. Accordingly, phenotypic changes were seen in the form of enhanced migration and invasion but unaltered proliferation. In addition, colony and spheroid formation was increased after specific Notch-3 silencing. The simultaneous knock down of Notch-1 and -3 showed no additive effect. Conclusion: Our results provide evidence that Notch-1 and Notch-3 are involved in invasion and progression of BCA by maintaining an epithelial phenotype and inhibiting EMT and self-renewal potential. This is the opposite of what we have seen previously with Notch-2. Beside verification of our observations in metastatic xenograft models, further investigation is needed to elucidate the molecular mechanisms of these alterations. Citation Format: Wolfgang Jaeger, Tetsutaro Hayashi, Shannon Awrey, Kilian Gust, Thomas Cordonnier, Na Li, Ralph Buttyan, Estelle Li, Ladan Fazli, Theodorus Van Der Kwast, Bas W. G. Van Rhijn, Peter C. Black. Silencing Notch-1 and Notch-3 promotes epithelial-to-mesenchymal transition (EMT) and self-renewal potential in human bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1494. doi:10.1158/1538-7445.AM2013-1494
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».