Oncogenic Regulation of Tissue Factor Expression
Notice bibliographique
Résumé
Abstract Abstract SCI-16 Coagulation system plays a long-recognized role in cancer progression and in the related morbidity and mortality (1, 2). Once regarded as an unspecific epiphenomenon of the underlying disease, this involvement is now viewed as a direct consequence of oncogenic mutations and the resulting acquisition of the procoagulant phenotype by cancer cells followed by local and systemic vascular consequences (Trousseau syndrome) (3). Tissue factor (TF) represents an illuminating molecular paradigm of these changes, acting as both the central regulator of the coagulation system circuitry and an emerging regulatory target of several oncogenic lesions. Thus, oncogene-driven TF upregulation has been documented in a wide spectrum of human cancer cells, including: colorectal (CRC), lung, breast, and skin cancer, as well as glioblastoma (GBM), medulloblastoma (MB), and hematopoietic malignancies. This is linked to activation of several dominant acting oncogenes, such as: K-ras, epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), HER-2, MET, retinoid acid receptor (RAR), and several others (4). These effects are also enabled and amplified by losses of tumor suppressor genes, such as p53 and PTEN, and modulated by microRNA (miR) networks, as well as microenvironmental and regulatory factors, such as hypoxia, inflammation, differentiation, and epithelial-to-mesenchymal transition (EMT) (5). In addition, oncogenic mutations activate several mechanisms that may sensitize cancer cells to extracellular stimuli, including the exposure to circulating coagulation factors that may access cancer cells through leaky tumor blood vessels. For instance, the expression of EGFRvIII in human GBM cells leads not only to a dramatic increase in TF levels, but also to the ectopic expression of coagulation factor VII, the main TF ligand. Simultaneously, oncogenic events (e.g., EGFRvIII or K-ras) induce marked upregulation of protease activated receptors 1 and 2 (PAR1/2), which further enhance the transmission of intracellular signals from the TF/FVIIa complex (6). Furthermore, oncogenes provoke cellular vesiculation whereby TF and other signaling proteins (including oncoproteins themselves) are released into the extracellular space and to the systemic circulation. As a result, these signaling proteins may be transferred to other cells, and modify their properties locally, regionally, and systemically (4, 7). These changes are a part of the signaling network that affects tumor growth, invasion, and metastasis, and acts through generation of a procoagulant, proinflammatory, and pro-angiogenic microenvironment, which contain niches for tumor-initiating cells (TICs). TICs (cancer stem cells) are key targets for oncogenic transformation and essential drivers of the malignant process. Their responses to the coagulation system may be altered by changes in TF and PAR status. TF targeting through genetic and pharmacological approaches results in impaired tumor initiation and growth in various experimental settings, including in transgenic models of GBM. In some instances host cell-associated TF may also play a role in disease progression, while in other cases tumor stroma and inflammatory cells are modulated indirectly by TF-expressing cancer cells (7). Collectively, oncogene-dependent deregulation of TF and activation of the coagulation system circuitry represents a unique biological effector mechanism, which likely promotes progression of human cancers, and thereby may serve as a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.
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) | 0,006 | 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 ».