The KDELR3 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with disruption of the human KDELR3 gene. This loss-of-function model enables studies of KDEL receptor 3 in ER-Golgi retrograde transport. The polyclonal nature provides a heterogeneous edited pool, avoiding clonal selection bias, and is suited for robust functional analyses of secretory pathway dynamics and ER homeostasis in a liver-derived context.
Built on the SK-HEP-1 host line derived from the ascites of a liver adenocarcinoma patient, these cells display a dual epithelial-endothelial phenotype. SK-HEP-1 is a widely used model for hepatic sinusoidal endothelium and hepatocellular carcinoma, capable of tumor formation in xenografts while retaining hallmark liver cancer signaling. Introducing KDELR3 knockout in this context provides a targeted platform to study ER-associated processes within liver cancer biology.
KDELR3 encodes a transmembrane receptor that cycles between the Golgi and ER, binding KDEL-bearing chaperones such as BiP (HSPA5) and calreticulin (CALR) in the Golgi and mediating their COPI-dependent retrograde retrieval. This process maintains ER folding capacity and is integrated with the unfolded protein response (UPR). KDELR3 expression is regulated by ER stress sensors ATF6, IRE1, and PERK, and the transcription factors ATF4 and XBP1. Downstream, it sustains ER chaperones including HSPA5, CALR, P4HB, and PDIA3. The receptor interacts directly with COPI components ARF1 and COPA, and its trafficking is modulated by GOLPH3, establishing a key node in ER-Golgi communication.
In SK-HEP-1 liver adenocarcinoma cells, KDELR3 knockout provides insight into ER stress-related pathologies such as hepatocellular carcinoma. These cells encounter proteotoxic stress from high secretory demands, and the UPR supports survival and drug resistance. Disrupting KDELR3 compromises chaperone retrieval, potentially inducing chronic ER stress and chemosensitization. SK-HEP-1 cells are also permissive to SARS-CoV-2, and KDELR3’s role in the viral life cycle makes this model relevant for studying infection-triggered ER remodeling. Thus, this model uniquely integrates ER cell biology with cancer and infectious disease research.
This knockout cell population supports diverse applications, including ER-Golgi trafficking analysis, UPR activation monitoring via RT-qPCR of targets like HSPA5 and CALR, and protein retention assays by immunofluorescence or flow cytometry. Western blotting for KDELR3 and client chaperones validates the knockout, while ER stress reporters enable quantitative pathway assessment. The cells are also suited for cell viability assays to test drug sensitivity and for measuring protein secretion kinetics. For ordering details and technical support, please contact Ascent Research.
