The JAGN1 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human liver adenocarcinoma epithelial cell line. This product features targeted disruption of the JAGN1 gene, generating a heterogeneous pool of loss-of-function mutations that eliminate JAGN1 protein expression. Suitable for advanced research, these polyclonal cells provide a physiologically relevant model without the constraints of single-cell cloning, capturing the biological variability inherent in polyclonal editing for robust functional studies.
The SK-HEP-1 host cell line was established from ascitic fluid of a 52-year-old male with liver adenocarcinoma. These adherent epithelial cells are tumorigenic and widely used as an in vitro model for hepatocellular carcinoma (HCC), permitting investigation of cancer signaling, EMT, and therapy resistance. Their intact secretory pathway and ER architecture make them an optimal system for studying JAGN1??s role in ER homeostasis within a malignant liver context.
JAGN1 encodes an ER membrane protein that facilitates the transition from COPII to COPI vesicle coats, interacting with COPA, COPB1, COPB2, and LMAN1 to maintain ER structure and secretion. It operates downstream of ER stress sensors ATF6 and XBP1 and is modulated by G-CSF and inflammatory cytokines. Loss of JAGN1 disrupts glycosylation and trafficking, upregulating HSPA5/BiP and causing ER stress. This disrupts neutrophil development by impairing secretion of neutrophil elastase, leading to severe congenital neutropenia. Key pathway partners include SEC23A, SAR1B, and HSPA5.
In SK-HEP-1 cells, JAGN1 knockout illuminates the link between ER proteostasis and HCC progression. Tumor cell proliferation and metastasis often depend on enhanced secretory capacity; JAGN1 disruption may expose vulnerabilities in this machinery. This model enables study of ER stress-mediated signaling via ATF6 and XBP1 and its crosstalk with oncogenic pathways. As a polyclonal population, it reflects heterogeneous cancer cell responses and can serve as a control for neutrophil-relevant assays in the tumor microenvironment.
Applications include mechanistic studies of congenital neutropenia using western blotting for HSPA5 and RT-qPCR for COPI components. In HCC research, the cells support migration/invasion, apoptosis, and drug sensitivity assays to screen secretory-pathway-targeted therapies. Flow cytometry and immunofluorescence assess ER stress markers and morphology. This versatile tool facilitates dissection of ER-to-Golgi trafficking defects and accelerates drug discovery for neutropenia and liver cancer. For further technical information, please contact Ascent Research.
