Abstract 6002: Increased ferroptosis sensitivity and epithelial to mesenchymal transition of breast cancer cells overcoming chemotherapeutic mediated apoptotic caspase activation
Notice bibliographique
Résumé
Abstract The survival of cancer cells post chemotherapeutic treatment can lead to the presence of recurrent tumors and continues to be a barrier to effective cancer treatment. The majority of chemotherapeutics kill cells through the induction of executioner caspases and subsequent apoptotic death, and resistance to apoptosis can lead to the presence of anastatic cancer cells. Executioner caspase release was previously thought to be the point of no return from apoptotic cell death, however, it has been shown that removal of the reagent causing caspase release can lead to recovery of cells from apoptotic signaling, a phenomenon which has been termed ``Anastasis``. This presents a need for a better understanding of the underlying mechanisms behind cancer cell survival and the mechanisms that lead to cell recovery and recurrent tumors. We have hypothesized that when treated with chemotherapeutics, some cells will evade cell death even when executioner caspases have been activated. By identifying surviving anastatic cells and the pathways involved in their evasion of cell death, we hope to propose novel therapeutic strategies to prevent their survival. The novel CasExpress system, developed by the Denise Montell lab group, was used to identify and isolate a population of cells surviving caspase-3 activation as a result of chemotherapeutic treatment in Triple Negative Breast Cancer (TNBC) cell lines. The CasExpress system permanently labels these cells with GFP post caspase-3 activation. Analysis of this population of SUM159 anastatic cells, identified by their GFP expression, demonstrates that these cells have an increased resistance to further chemotherapeutic treatment, a decrease in levels of active caspase-3, an up-regulation of Cancer Stem Cell marker CD44, and a more mesenchymal phenotype. Furthermore, these “anastatic cells” express decreased levels of GPX-4, an enzyme that mitigates ferroptosis via lipid peroxide reduction, and are more sensitive to GPX-4 and xCT inhibitor mediated ferroptosis cell death.To investigate the link between Epithelial to Mesenchymal Transition (EMT) and ferroptosis mediated cell death, we used TGF-b to stimulate EMT in NMe mouse epithelial cells. We found that TGF-b induced EMT is associated with increased sensitivity to ferroptosis mediated by GPX-4 inhibition. Furthermore, the TGF-b induced EMT cells have a marked decrease in the expression of GPX4, similar to what was observed in the TNBC anastatic cells. These results indicate a potential link between EMT and an increased sensitivity to ferroptosis, and provide novel strategies for identifying and targeting chemotherapeutic resistant tumor cells. Citation Format: Rachel Hausman, Wells Brown, Paul McDonald, Shannon Awrey, Gongping Sun, Denise Montell, Shoukat Dedhar. Increased ferroptosis sensitivity and epithelial to mesenchymal transition of breast cancer cells overcoming chemotherapeutic mediated apoptotic caspase activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6002.
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) | 0,000 | 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) | 0,003 | 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 ».