Abstract 1087: Semaphorin 3C drives invasiveness in prostate cells through epithelial-to-mesenchymal transition and stemness
Notice bibliographique
Résumé
Abstract Our work sets out to show that semaphorin 3C is a driver of epithelial-to-mesenchymal transition and stemness in prostate cancer. Prostate cancer (PCa) is among the most commonly-occurring non-cutaneous cancers in men. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted chemotactic proteins whose normal functions reside in embryogenesis and development where they are responsible for directing cell movement. Semaphorins act through autocrine, paracrine, and juxtacrine signaling and have been implicated in a broad range of biological functions ranging from tissue morphogenesis to immunity; altered semaphorin expression has also been observed in numerous cancers. One member of the class 3 semaphorins, semaphorin 3C (SEMA3C), has been implicated in several forms of cancer and its increased expression is correlated with prostate cancer severity. Additionally, SEMA3C has been shown to be upregulated in response to chemotherapy and radiation treatment, promote metastasis to the lung, and promote tumourigenicity of glioma cells. SEMA3C has also been documented to increase cell proliferation and migration, decrease apoptosis, and promote integrin signaling and VEGF secretion in endothelial cells. SEMA3C was shown to drive migration of breast cancer cells and recent studies have highlighted the importance and prognostic value of SEMA3C in prostate cancer. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes cancer progression by driving mesenchymal and stem-like phenotypes. Other class 3 semaphorins have been shown to drive EMT and the link between SEMA3C and stemness has been established in glioma cells. In the present study, using gain of function studies coupled to gene expression (qPCR, Western blot, FACS, immunofluorescence microscopy) and functional studies (migration, invasion, and sphere-forming assays) we show that ectopic expression of SEMA3C in RWPE-1, a normal prostate epithelial cell line, promotes epithelial-to-mesenchymal transition and stemness. Specifically, we find that overexpression of SEMA3C leads to an upregulation of EMT markers and migratory and invasive phenotypes. SEMA3C overexpression was also associated with an upregulation of the cancer stem cell marker, CD44, and heightened sphere-forming capabilities. Additionally, using ultrasound-guided intracardiac injection of SEMA3C-overexpressing cells, we show that SEMA3C drives cell dissemination in vivo. We conclude from our studies that SEMA3C is a driver of prostate cancer by promoting epithelial-to-mesenchymal transition and stemness. Citation Format: Kevin J. Tam, Daniel H. Hui, Wilson C. Lee, Mingshu Dong, Tabitha Tombe, Ivy Z. Jiao, Shahram Khosravi, Ario Takeuchi, James W. Peacock, Larissa Ivanova, Igor Moskalev, Martin E. Gleave, Ralph Buttyan, Michael E. Cox, Christopher J. Ong. Semaphorin 3C drives invasiveness in prostate cells through epithelial-to-mesenchymal transition and stemness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1087.
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 | 0,001 |
| 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 ».