Abstract 5160: Claudin1 induces cell motility and invasion through PI3K/Akt/NFkB signaling in keratin-depleted carcinoma cell lines.
Notice bibliographique
Résumé
Abstract In the early steps of metastasis, carcinoma cells undergo through a dedifferentiation process called ‘epithelial-mesenchymal transition’ (EMT). Among all phenotypic changes associated with this transition, the reduction or loss of keratin expression is often considered as a histological and biochemical feature for tumor cells that are going through an EMT. Keratins are epithelial-specific intermediate filament proteins which are expressed in a tissue-specific manner. Keratins 8 and 18 (K8/18) are typically co-expressed as the primary keratin pair in simple epithelial cells and their expression is maintained during malignant transformation until the tumor become invasive. As part of the cytoskeleton, keratins are important for the integrity of epithelial cells and tissues. Moreover, a number of keratins are involved in intracellular signaling pathways which regulates cell growth and death. In recent years, studies provided evidence that keratins should not be considered only as markers but also as regulators of cancer cell signaling.In the present study, we investigated whether K8/18 expression play an active role in EMT. We used RNA interference approach targeted against K8/18 to mimic keratin loss during EMT in two different epithelial cancer cell lines. Using in vitro wound healing and matrigel invasion assays, we observed that K8/18 stable knockdown increases collective migration and invasiveness of epithelial cancer cells without modulating EMT markers. Interestingly, we identified the tight junction protein claudin1 as a regulator of these processes. Indeed, claudin1 is highly increased and mislocalized in K8/18-depleted cells and it promotes membrane targeting and activation of Akt1 and Akt3. Claudin1 also induces NFkB nuclear translocation in a PI3K dependent manner. Therefore, NFkB transcriptional activity is increased in K8/18-knockdown cells as shown by luciferase reporter assay, leading to MMP2 and MMP9 expression. This led to our proposal of a model in which K8/18 loss promotes collective migration of epithelial cancer cell in a different way than an EMT, by increasing directional migration and intercellular cohesion. At the leading edge of the migrating cell sheet, K8/18 loss improves PI3K/Akt activation involved in the direction of movement and local matrix degradation through NFkB activity. In the following rows, K8/18 knockdown increases claudin1 at the cell membrane which strengthens cell cohesion.To our knowledge, these results represent the first indication that K8/18 can influence the phenotype of epithelial cancer cells at a transcriptional level and strongly indicate that in cancer, keratins should not be considered only as markers of differentiation but also as key regulators in cancer progression. Citation Format: Anne-Marie Fortier, Monique Cadrin, Eric Asselin. Claudin1 induces cell motility and invasion through PI3K/Akt/NFkB signaling in keratin-depleted carcinoma cell lines. [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 5160. doi:10.1158/1538-7445.AM2013-5160
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 | 0,001 |
| 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 ».