Biomarker: Jag1

Histology type: endometrial carcinoma

Region: Thessaloniki

Followed up time : median follow-up of 72 month

Description: Aberrant expression of key components of the Notch and Hedgehog signaling pathways, as well as MMRd may serve as independent prognostic factors for recurrence and survival in patients with endometrial cancer.

Sample type : tissue

Statictics: Mean;Range

Cohort age: 63.9;29–87

Survival figure legend: Evaluation of Jag1-Notch pathway activation patterns.

Survival figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283658/figure/pone.0208221.g003/

Expression figure legend: Characteristic examples of negative and positive protein markers with IHC.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283658/figure/pone.0208221.g002/

Description: The Notch pathway regulates cell proliferation, cell fate, differentiation, and cell death in all metazoans. Notch itself is a cell-surface receptor that transduces short-range signals by interacting with transmembrane ligands such as Delta (termed Delta-like in humans) and Serrate (termed Jagged in humans) on neighboring cells. Some soluble ligands have also been identified in Caenorhabditis elegans, but these bind to Notch together with transmembrane adaptors (Komatsu et al. 2008). Ligand binding leads to cleavage and release of the Notch intracellular domain (NICD), which then travels to the nucleus to regulate transcriptional complexes containing the DNA-binding protein CBF1/RBPjk/Su(H)/Lag1 (CSL).Following their synthesis, Notch receptors are cleaved by protein convertases during exocytosis at site 1 (S1), which regulates their trafficking and signaling activity (Logeat et al. 1998; Gordon et al. 2009). During passage through the Golgi, they can be glycosylated by glycosyltransferases such as Fringe, which determines the subsequent response to different subfamilies of ligands. These and other posttranslational modifications of the receptors and ligands tune the amplitude and timing of Notch activity to generate context-specific signals. Several proteins, including E3 ubiquitin ligases (e.g., Deltex and Nedd4), Numb, and α-adaptin, regulate the steady-state levels of the Notch receptor at the cell surface. In signal-sending cells, E3 ubiquitin ligases (Neur and MIB) similarly ubiquitylate the intracellular domain of the ligand to promote epsin-mediated endocytosis, which is associated with ligand activation .[PMC3475170]