JAG1 (Jagged Canonical Notch Ligand 1)

In addition to these mechanisms, Notch2 acts as a transcription factor that directly controls the expression of key targets, such as CD23 and Hes1, that are fundamental for B cell proliferation, differentiation, and survival in CLL. All of these circuits represent important therapeutic targets and help explain the cells' dependence on their niche, the formation of proliferation centers, and resistance to modern targeted agents.

This study provides new insights into the gene expression profile of thyroid CSC-like cells and their interactions with cells constituting tumor tissues.

Future treatment strategies should prioritize precision medicine, including subtype-specific Notch receptor inhibitors, biomarker-driven personalized therapies, and combination treatments aimed at modifying the tumor microenvironment. A thorough understanding of these dual roles is significant for developing more accurate and effective treatment approaches for digestive system cancers.

Conversely, Jag1 overexpression augments TIC self-renewal. Thus, Jagged1-mediated Notch signaling controls a hybrid-EMT state that is a defining feature of TICs in PDAC.

Activation of Jag1/Notch1/Hes1 signaling pathway protects the intestinal mucosal barrier from inflammatory injury by abrogating MLCK-dependent TJ dysregulation.

These findings uncover a zinc-dependent ZFP36L1-regulon that governs hepatocyte fate by repressing p21- and JAG1-driven senescence and NOTCH activation and highlight ZFP36L1 as a promising therapeutic target in ALD.

Paclitaxel-induced translational upregulation of NOTCH2 enables immediate juxtacrine activation by JAG1-positive macrophages, coupling tumor cell survival with immune remodeling in the tumor microenvironment to drive chemoresistance. Our results suggest NOTCH2 is a viable biomarker for paclitaxel resistance and that combining NOTCH2 inhibitor with taxane is an effective therapeutic strategy to selectively disrupt tumor-macrophage interaction and overcome macrophage-mediated taxane resistance in NOTCH2-positive tumors.

Este estudio proporciona el primer vínculo mecanístico entre los niveles de prolactina durante el embarazo y el aumento de la agresividad del CRC a través de la señalización JAK2/STAT3 y JAG1/NOTCH1. También sugerimos una nueva dirección terapéutica al demostrar que la PRL sensibiliza las células de CRC a la apoptosis inducida por TRAIL. En conjunto, el estudio subraya la necesidad de nuevas estrategias terapéuticas para el tratamiento seguro y eficaz del CRC en pacientes embarazadas.

Taken together, the two opposite signaling effects of SHP2 suggest that both the immune and vascular system responses appear to be more modulated by the redox, cell, and compartment-specific signaling of SHP2. More studies are needed for mitigating cardiovascular toxicity to patients, particularly with ICI-based treatment regimens.

Our HKO model advances our understanding of renal tumorigenesis in the context of the trajectory of nephron development. Implications: Dysregulated nephron developmental machinery leads to aberrant cell proliferations of immature renal tubules.

Our findings underscore the pivotal role of CD146+ CAFs in shaping an immunosuppressive microenvironment and highlight CD146+ CAFs and COL4A1 as promising candidates for targeted therapy in gastric cancer.

Clinically, the Notch ligand JAG1 was upregulated in recurrent high-grade glioma patients treated with the oHSV CAN-3110 and correlated with poor prognosis. Heightened EGFR activation in senescent cells was a mechanism to escape cell death, which created a unique opportunity for cetuximab as a senolytic agent. Combination therapy reduced EGFR signaling and induced macrophage-mediated antibody-dependent cellular cytotoxicity, thereby increasing the anti-tumor therapeutic efficacy of OD-0J1.