Abstract 1484: Inhibition of the glycosylation enzyme Mgat1 blocks migration, invasion and metastasis of malignant cells
Notice bibliographique
Résumé
Abstract N-acetylglucosaminyltransferase I (Mgat1) is the enzyme that initiates the biosynthesis of hybrid and complex N-glycans in medial golgi. As such, it regulates N-glycosylation, a post-translational modification that alters the localization and function of cell surface proteins. Aberrant activity of the N-glycosylation pathway is seen frequently in malignant cells and contributes to their metastatic potential. Here, we have evaluated the effects of Mgat1 inhibition in malignant cells. We knocked down Mgat1 with two independent shRNA in Hela human cervical cancer cells. Target knockdown and inhibition was confirmed by demonstrating mRNA knockdown, decreased cell-surface lectin staining, and inhibition of enzymatic activity. Knockdown of Mgat1 did not induce cell death or inhibit proliferation. Complex N-glycans influence cell migration and invasion. Therefore, we investigated the effect of Mgat1 knockdown on these glycosylation-mediated processes. Hela cells with Mgat1 knockdown and control shRNA were seeded into invasion chambers. Twenty four hours after seeding, we measured cell migration through uncoated chambers and cell invasion through Matrigel-coated chambers. Compared to control shRNA, Mgat1 knockdown significantly decreased Hela cells migration and invasion. ιntegrins influence cell migration and invasion and are N-glycosylated. Therefore, to begin to understand the mechanism by which Mgat1 knockdown inhibits cell migration and invasion, we examined changes in the cell surface expression of β1 integrins. By confocal microscopy, knockdown of Mgat1 decreased cell surface expression of β1 integrins and increased their localization around the nucleus. To assess the effects of Mgat1 on metastasis in vivo, we knocked down Mgat1 with shRNA in RFP-labeled PC3N7 prostate cancer cells. Mgat1 knockdown or control cells were then injected orthotopically into the prostate gland of sublethally irradiated SCID mice. Four weeks after injection, mice were sacrificed and distant tumor formation was imaged with fluorescent microscopy. Mgat1 knockdown decreased the median number of tumors that had metastasized to the lung more than three-fold compared to control. Our preclinical studies, suggest a role for Mgat1 in cancer cell metastasis. Therefore, we examined the association between Mgat1 mRNA expression in primary tumors and the incidence of subsequent metastasis. By analyzing publically available gene expression array data sets from patients with breast cancer, we determined that patients with the lowest levels of Mgat1 mRNA in their primary tumors were least likely to develop metastatic disease after therapy. In summary, this work highlights the role of the N-glycosyltransferase Mgat1 in cancer cell metastasis. As such, Mgat1 may be a novel target for anti-cancer therapies and levels of Mgat1 in primary tumors may help predict the risk of developing metastatic disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1484. doi:10.1158/1538-7445.AM2011-1484
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) | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».