Abstract B009: A role for receptor tyrosine kinase crosstalk in a Met-dependent model of triple-negative breast cancer
Notice bibliographique
Résumé
Abstract Triple-negative (TN) breast cancers, which include the basal-like and claudin-low subtypes, account for up to 20% of breast cancer cases. TN breast cancers lack expression of therapeutic targets HER2 and estrogen receptors and are correlated with poor prognosis. In human breast cancer, elevated levels of MET are correlated with TN subtypes and poor outcome. The Met receptor tyrosine kinase (RTK) is a cell surface protein that, upon activation by its ligand hepatocyte growth factor (HGF), initiates a program of cell survival, migration, and invasive growth. To investigate the role of Met in breast tumorigenesis, we have used two mouse models in which mammary specific expression of an oncogenic variant of Met is driven by the MMTV promoter (Metmt). Metmt mice develop mammary tumors with a long latency and display features of basal-like breast cancer. As loss of function mutations in TP53 are found in ~80% of TN breast cancers, we have also generated Metmt mice with conditional deletion of Trp53 in the mammary gland (Metmt;p53-), which results in accelerated tumorigenesis and gene expression profiles that more closely resemble that of the claudin-low subtype of TN breast cancer. The present work aims to elucidate how Met promotes mammary tumor development and whether this involves regulation of tumor-initiating cells (TICs). TICs have emerged as a key concept in prevailing models of tumor development, and are thought to drive tumorigenesis as well as contribute to disease relapse. To study TICs in our mouse models, we employed the sphere-forming assay, which enriches for TICs based on their stem-like ability to survive, propagate, and self-renew in suspension as spheroid structures (tumorspheres). Tumorspheres cultured from both tumor models express constitutively active Met. Upon treatment with Met inhibitor, Metmt tumorspheres are drastically reduced in both number and size. In contrast, Metmt;p53- tumorspheres are insensitive to Met inhibition, suggesting that other signals compensate for the loss of Met activity. It has been shown that Met can crosstalk with other RTKs such as EGFR. Therefore we hypothesize that activation of an alternative RTK signalling pathway is compensating for loss of Met signalling in Metmt;p53- tumorspheres. The molecular events that lead to TN breast cancers are poorly understood. Validating a role for Met in TICs and identifying key cooperating pathways involved in the pathogenesis of triple negative breast cancers could provide information for new therapeutic targets. Citation Format: Vanessa Sung, Jennifer F. Knight, Morag Park. A role for receptor tyrosine kinase crosstalk in a Met-dependent model of triple-negative breast cancer. [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 B009.
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) | 0,001 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».