The KDELR1 Knockout NCI-H1975 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population targeting KDELR1 in the human NCI-H1975 cell line. This loss-of-function model is generated through CRISPR/Cas9-mediated gene disruption, yielding a heterogeneous knockout population ideal for studying KDELR1 deficiency without clonal selection artifacts.
The host cell line, NCI-H1975, is a human lung adenocarcinoma epithelial cell line harboring both EGFR L858R activating and T790M resistance mutations. It serves as a well-established model for non-small cell lung cancer (NSCLC), widely used to investigate EGFR signaling, tyrosine kinase inhibitor resistance, and lung cancer biology.
KDELR1 encodes KDEL receptor 1, a seven-transmembrane receptor that mediates retrograde transport of escaped ER-resident chaperones from the Golgi back to the ER via COPI vesicles. It is regulated by ER stress stimuli such as tunicamycin and thapsigargin and by transcription factors XBP1 and ATF4. KDELR1 interacts with KDEL-containing cargo proteins, the COPI complex (including ARF1 and TMED2/p24), and retrieves key chaperones like BiP (HSPA5), Calreticulin, and PDI (P4HB). Knockout disrupts this retrieval, causing accumulation of unfolded proteins, activation of the unfolded protein response (UPR), and engagement of ER-associated degradation (ERAD).
In NCI-H1975 NSCLC cells, KDELR1 knockout enables dissection of how ER-Golgi trafficking defects intersect with oncogenic EGFR signaling and cellular stress adaptation. The double-mutant EGFR background may alter UPR sensitivity, offering a platform to identify synthetic lethal interactions or evaluate therapeutic strategies targeting protein homeostasis in lung adenocarcinoma.
This model supports applications in ER-Golgi trafficking studies, ER stress signaling in cancer, KDELR-dependent viral entry (e.g., SARS-CoV-2, dengue), and drug target discovery for protein-trafficking diseases. Compatible assays include western blotting for BiP and spliced XBP1, immunofluorescence of KDELR1 and Golgi markers (e.g., Golgin-97), RT-qPCR of UPR genes, Gaussia luciferase secretion assays, co-immunoprecipitation with ARF1, and cell viability assays under ER stress. For further information, please contact Ascent Research.
