Abstract A091: Ezrin functions as a metastasis-associated protein by regulating multiple steps involved in breast cancer cell dissemination
Notice bibliographique
Résumé
Abstract The membrane cytoskeleton cross-linker ezrin, is frequently up-regulated in many aggressive cancer types including breast, and is linked to metastatic progression. However, the underlying molecular mechanisms that delineate how ezrin may be involved in the cancer cell dissemination process remain unclear. In this study, we sought to determine the precise role of ezrin in several key components of the metastatic cascade, namely angiogenesis, cell migration, invasion, and lung seeding, in order to gain a comprehensive understanding of the function of ezrin as a metastasis-associated protein. By depleting ezrin expression in MDA-MB-231 invasive breast carcinoma cells, we demonstrate using ex vivo aortic ring and in vivo Matrigel plug assays that ezrin is required for promoting angiogenesis, thereby providing a critical escape route for tumor cells. We further show that the endogenous levels of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic regulator, are significantly reduced in ezrin-depleted cells. Interestingly, secretion of interleukin-6 (IL-6), a known regulator of VEGF-A expression and myeloid cell recruitment, and activation of its downstream effector signal transducer and activator of transcription 3 (Stat3) were also markedly inhibited in these cells, thus suggesting a critical role for ezrin in mediating angiogenesis and potentially pre-metastatic niche priming. Using real-time microscopy, we found that ezrin-deficient cells displayed impaired focal adhesion and invadopodia dynamics, resulting in increased cell-ECM attachment, reduced migration and invasion, though no change in proteolysis was observed. Furthermore, ezrin-depleted cells exhibited significantly less directionality in their movement and were defective in their ability to migrate through an endothelial cell barrier by affecting tight junction permeability. These findings suggest that ezrin may be involved in facilitating intra/extravasation. One of the final stages of cancer cell dissemination is colonization at a distant organ site. Indeed, in vivo lung seeding experiments revealed that fewer ezrin-depleted cells remained in the lung 24 h post-injection, and ultimately led to a reduction in the number of tumor nodules. Collectively, our results unveil a novel coordinate role for ezrin in regulating metastatic progression, and provide important insight in evaluating ezrin as a potential prognostic/predictive marker for metastatic relapse in human breast cancers. (Supported by Canadian Institutes of Health Research, CIHR; Canadian Breast Cancer Foundation Doctoral Fellowship Program; and the Terry Fox Training Program in Transdisciplinary Cancer Research). Citation Format: Victoria Hoskin, Abdi Ghaffari, Alvin Szeto, Bruce E. Elliott. Ezrin functions as a metastasis-associated protein by regulating multiple steps involved in breast cancer cell dissemination. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A091.
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 | 0,001 |
| 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) | 0,001 | 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 ».