The JAG1 Knockout HGC-27 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal cell population derived from the HGC-27 human gastric cancer cell line, with targeted disruption of the JAG1 gene. This knockout model eliminates functional Jagged1 protein across a heterogeneous pool, providing a consistent loss-of-function background for Notch signaling studies. As a polyclonal population, it avoids clonal artifacts and maintains tumor cell diversity, ensuring reproducible experimental outcomes without single-cell clone bias.
The parental HGC-27 line is an epithelial cell model established from a metastatic lymph node of a patient with poorly differentiated gastric adenocarcinoma. It retains aggressive features such as high metastatic potential and aberrant developmental signaling, making it clinically relevant for investigating molecular mechanisms of gastric cancer dissemination and tumor microenvironment interactions.
JAG1 encodes the Notch ligand Jagged1, which engages NOTCH1, NOTCH2, and NOTCH3 receptors to trigger ADAM17- and gamma-secretase-mediated release of the Notch intracellular domain (NICD). NICD complexes with CSL/RBPJ and MAML1 to activate transcription of HES1, HEY1, MYC, CCND1, and SNAI1. JAG1 expression is regulated by NF-??B, TGF-??/SMAD, and hypoxia/HIF-1??, with feedback from NICD. Disruption of JAG1 therefore abolishes ligand-dependent Notch activation, reducing target gene expression and impairing proliferative, anti-apoptotic, and EMT programs.
In HGC-27 gastric cancer cells, Jagged1-driven Notch signaling promotes malignant phenotypes including proliferation, survival, and invasion. This knockout model enables dissection of Jagged1-specific contributions to the poorly differentiated state, metastatic traits, and stromal cross-talk. It is particularly valuable for studying JAG1 interactions with EMT regulators like SNAI1 and for identifying therapeutic vulnerabilities upon Notch pathway inhibition.
Key applications include mechanistic studies of Jagged1-dependent Notch signaling in gastric cancer progression and metastasis, using assays such as western blotting and RT-qPCR for HES1/HEY1, proliferation assays, flow cytometry for apoptosis/cell cycle, and transwell migration/invasion. Co-culture with Notch reporter cells can quantify ligand-dependent signaling. This model also supports drug resistance screening and synthetic lethality studies. For more information, contact Ascent Research.
