Abstract 4968: Msi2 directly linked to Hedgehog and Wnt signaling in non-triple negative breast cancer
Notice bibliographique
Résumé
Abstract Introduction: Previously, we have shown that a gain on 17q22.24.2 was a predictor of invasiveness when found in duct carcinoma in situ (DCIS) and of nodal metastasis when found in invasive duct carcinoma (IDC). Within this amplicon, we have identified a gene that is a likely driver of breast tumorigenesis and progression: Musashi homolog 2 (Msi2). Msi2 has a functional role in neural stem cell maintenance and regulation of hematopoietic stem cells. Previously, Msi2 has been implicated in Notch and Hedgehog signaling in leukemia, and here we link Msi2 to an increase in Wnt activation. Methodology: To understand the expression of Msi2 in patient tissue, tissue microarrays (TMAs) containing 232 breast cancers were analyzed by immunohistochemistry. MDA-MB-231 and MCF7 cells expressing Msi2-GFP and GFP clones were plated on transwells to examine cell migration and invasiveness. Proliferation was analyzed by the MTS assay. TOP-FOP and Gli1 Luciferase assays were used to confirm activation of Hedgehog and Wnt signaling. Western blots were used to assess total beta-catenin levels in the cell lines. Analysis of publicly available expression microarray databases and RT-PCR of the over-expression cell lines validated the proposed mechanism of action. Results: Tissue microarrays confirmed that Allred scores for Msi2 significantly correlated with grade, size stage, and non-triple negative receptor status. Over-expression of Msi2, in MDA-MB-231 (triple negative) and MCF7 (luminal cell type with epithelial morphology) cell lines, caused an increase in proliferation, migration and invasion. The knockdowns demonstrated the reverse effect. As determined by the TOP-FOP luciferase assay and RT-PCR, Msi2 leads to increased signaling of Hedgehog and Wnt. Furthermore, Msi2-mediated activation of Wnt occurs independently of total beta-catenin levels. Microarray analysis of breast cancer cell lines and patients' tumors supports this mechanism of action for Msi2 in non-triple negative cell lines (as assessed by Pearson's correlation coefficient of pathway interactions). Conclusion: When overexpressed in a cancerous cell system in vitro, Msi2 levels correlate with increased migratory and invasive capabilities. Furthermore, its implication in Notch, Hedgehog, and Wnt Signaling, make Msi2 a likely driver of the 17q22-24.2 amplicon in breast cancer. This study furthers our understanding of Msi2, and hints at the possibility that Msi2 plays a more significant role in cellular events and tumorigenesis than previously thought. Citation Format: Moustafa Abdalla, Nisha Kanwar, Yanglong Zhu, Ranju Nair, Bruce J. Youngson, Naomi A. Miller, Tianyu Liu, Susan J. Done. Msi2 directly linked to Hedgehog and Wnt signaling in non-triple negative breast cancer. [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 4968. doi:10.1158/1538-7445.AM2014-4968
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 | 0,000 | 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 ».