The EDEM2 Knockout SK-HEP-1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population in which the EDEM2 gene has been disrupted to create a loss-of-function model. This polyclonal pool, derived from the SK-HEP-1 host cell line, enables investigation of EDEM2-dependent endoplasmic reticulum (ER)-associated degradation (ERAD) without the use of single-cell cloning. The knockout cells are suited for functional studies of EDEM2 in a liver adenocarcinoma background and offer a reproducible system for dissecting glycoprotein quality control pathways.
The SK-HEP-1 cell line is a human liver adenocarcinoma-derived model originally established from the ascites of a patient. It displays a unique phenotype exhibiting both epithelial and endothelial characteristics, making it a versatile tool for hepatic tumor biology and vascular biology studies. The endothelial-like features of SK-HEP-1 allow for the interrogation of tumor microenvironment interactions, while its hepatic origin retains relevance to hepatocellular carcinoma research.
EDEM2 is an ER-resident lectin that recognizes mannose-trimmed N-glycans on misfolded glycoproteins, directing them to the ERAD pathway for retrotranslocation and proteasomal degradation. Its expression is transcriptionally activated by spliced XBP1 and ATF6, two key effectors of the unfolded protein response (UPR), and is further induced by ER stress agents such as tunicamycin or thapsigargin via the PERK?CATF4 axis. EDEM2 functions in concert with SEL1L, OS9, and the HRD1/SYVN1 E3 ubiquitin ligase complex, facilitating substrate delivery to the VCP/p97 retrotranslocation machinery. Knockout of EDEM2 disrupts this critical arm of ER quality control, leading to the accumulation of misfolded client proteins, including mutant alpha-1-antitrypsin, and potentially triggering sustained ER stress signaling.
In the SK-HEP-1 host cell context, loss of EDEM2 may perturb protein homeostasis and exacerbate ER stress, which is highly relevant to hepatocellular carcinoma biology, where altered ERAD and UPR signaling contribute to tumor progression and drug resistance. This model allows researchers to dissect how EDEM2 deficiency influences liver cancer cell viability, migration, and response to chemotherapeutic agents. The dual endothelial?Cepithelial nature of SK-HEP-1 also provides a platform to study the role of glycoprotein quality control in angiogenic-like phenotypes and tumor?Cstroma crosstalk.
This EDEM2 polyclonal knockout product is suitable for a wide range of applications, including mechanistic studies of ERAD through co-immunoprecipitation of EDEM2 interactors such as SEL1L and HRD1, analysis of UPR activation by Western blotting for CHOP, BiP, or phosphorylated eIF2??, and monitoring XBP1 splicing by RT-qPCR. Additionally, the cells can be used in drug sensitivity screens with ER stress inducers like tunicamycin and thapsigargin, flow cytometry-based viability assays under proteotoxic stress, and immunofluorescence imaging of ER morphology changes. For further information, please contact Ascent Research.
