The EDEM2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma cell line. This product provides a heterogeneous pool of cells with targeted disruption of the EDEM2 gene, enabling pooled loss-of-function studies. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, generating a mixed population that can be used directly in assays or further subcloned. EDEM2 encodes an ER degradation-enhancing alpha-mannosidase-like protein critical for monitoring glycoprotein folding.
The NCI-H1975 host cell line is a well-characterized model of non-small cell lung cancer (NSCLC), established from a patient with lung adenocarcinoma. These cells carry activating EGFR mutations L858R and T790M, the latter conferring resistance to first-generation tyrosine kinase inhibitors. This genetic background drives oncogenic signaling and makes NCI-H1975 a clinically relevant system for studying EGFR-mutant NSCLC biology and therapeutic vulnerabilities, including ER stress responses.
EDEM2 functions as a lectin in the endoplasmic reticulum (ER), recognizing mannose-trimmed N-glycans on misfolded glycoproteins to direct them to the ER-associated degradation (ERAD) pathway. It acts downstream of ER stress sensors IRE1??, PERK, and ATF6, and its expression is transcriptionally regulated by XBP1 and ATF6 under unfolded protein response (UPR) activation. EDEM2 interacts with OS9, XTP3-B, SEL1L, HRD1, and p97/VCP to facilitate retrotranslocation and ubiquitin-proteasome-mediated degradation. It collaborates with calnexin and calreticulin in glycoprotein quality control. Loss of EDEM2 impairs clearance of aggregation-prone proteins and dysregulates UPR signaling.
In the context of NCI-H1975 cells, EDEM2 knockout disrupts ER protein quality control, likely exacerbating basal ER stress heightened by oncogenic EGFR signaling. This model may reveal how compromised ERAD sensitizes lung adenocarcinoma cells to proteotoxic agents or UPR-targeted therapies. Since EGFR mutations can influence ER stress responses, EDEM2 loss-of-function allows dissection of the interplay between oncogenic signaling and proteostasis, potentially identifying synthetic lethal relationships or resistance mechanisms.
The EDEM2 Knockout NCI-H1975 Polyclonal Cells are suitable for investigating ERAD functions in EGFR-mutant NSCLC, studying ER stress responses, and screening proteostasis modulators. They support assays such as western blotting for BiP and CHOP, RT-qPCR for UPR targets, immunofluorescence for ER morphology, flow cytometry for viability, XBP1 splicing reporter assays, proteasome activity measurements, and TUNEL apoptosis detection. For further details or bulk inquiries, please contact Ascent Research.
