Abstract 1140: Par-4 mediates EMT in response to TGF-β stimulation
Notice bibliographique
Résumé
Abstract Endometrial cancer is the most common cancer affecting the female genital tract; this disease also stands as the fourth most frequent cancer affecting occidental women. Endometrial cancer is generally well manageable; however, the high metastatic potential of endometrial tumors represents one of the major hurdles in the treatment of this disease. The epithelial to mesenchymal transition (EMT) has been considered for a long time as a central mechanism by which cancer cells acquire invasive abilities necessary for metastasis formation. Multiple regulatory networks dictate this complex process; however TGF-β has been shown to be one of the most important inductor of EMT in cancer cells. Still, the process by which TGF-β induces this transition has yet to be fully understood. Our study demonstrates that TGF-β upregulates the expression of Par-4, a tumor suppressor protein concomitantly with the onset of EMT. Four uterine cell lines (Hec-1-a, KLE, HeLa, HIESC), one ovarian cell line (SKOV-3) and one breast cell line (MCF7) were used in this study. We first investigated the effect of exogenous TGF-β treatment on these cell lines to determine its effect on Par-4 expression. We've observed that TGF-β increased Par-4 levels in every cell lines. Preliminary analysis determined that this regulation was made through both Smad4 and p65, which was confirmed by the use of siRNA. We've also demonstrated that this regulation was made at the transcriptional level by RT-qPCR. We then sought to confirm the effect of TGF-β on our cell lines and its effect on EMT induction. Our experiments demonstrated that TGF-β promotes EMT as suggested by the upregulation of multiple EMT markers. Transfections using Par-4 expression plasmids induced similar changes, indicating the involvement of Par-4 in TGF-β mediated EMT induction. We then proceeded to assess the effect of Par-4 knockdown concurrent with exogenous TGF-β stimulation. This experiment revealed that Par-4 knockdown reduced the ability of TGF-β to induce Snail expression, further demonstrating the importance of Par-4 in the process of TGF-β mediated EMT. To conclude the study, we sought to understand the effect of XIAP in this process. Our experiments uncovered that XIAP regulates full length Par-4 levels through the inhibition of its caspase-mediated cleavage. Furthermore, the inhibition of XIAP by siRNAs, and thus of Par-4 cleavage, resulted in the reduction of Par-4 EMT inducing capabilities. In conclusion, our study proposes a novel function of Par-4 as an inductor of EMT in multiple cell lines. Citation Format: François Fabi, Parvesh Chaudhry, Mohan Singh, Eric Asselin. Par-4 mediates EMT in response to TGF-β stimulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1140. doi:10.1158/1538-7445.AM2014-1140
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 | 0,003 | 0,003 |
| 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) | 0,000 | 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 ».