The KDELR3 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population providing loss-of-function of KDEL receptor 3 in a human lung adenocarcinoma background. This heterogeneous pool of A-549 cells with targeted KDELR3 disruption enables functional studies without single-cell cloning, preserving population diversity. It is ideal for probing KDELR3’s role in ER protein retention and stress signaling.
A-549 cells, derived from a 58-year-old male lung adenocarcinoma, are adherent epithelial cells harboring a KRAS G12S mutation with wild-type p53 and EGFR. As a widely used lung cancer model, they provide a relevant platform to investigate ER homeostasis factors in tumor biology, making them suitable for studying KDELR3 in cancer cell adaptation.
KDELR3 encodes a Golgi-resident receptor that retrieves KDEL-bearing ER chaperones via COPI vesicles, a process requiring ARF1 and GBF1. This retrograde transport sustains ER proteostasis and counters the unfolded protein response (UPR). Under ER stress, sensors ATF6, IRE1, and PERK activate pathways driving XBP1-mediated transcription of BiP and calreticulin. KDELR3 thus attenuates UPR by reclaiming leaked ER proteins; its disruption is expected to trigger sustained UPR and ER stress, with downstream effects on cell survival.
In A-549 adenocarcinoma cells, KDELR3 disruption models ER stress vulnerability in a KRAS-mutant background. These polyclonal knockout cells allow examination of how loss of ER-Golgi retrieval influences UPR activation, apoptosis, and drug sensitivity. They are suited for investigating connections between ER proteostasis and oncogenic signaling, and for discovering synthetic lethal partners in lung cancer.
Applications include western blotting for BiP and CHOP, RT-qPCR of UPR genes, and immunofluorescence tracking of ER protein mislocalization. ER stress reporters, viability assays, and flow cytometry for apoptosis enable functional readouts. The polyclonal nature avoids clonal bias, ensuring robust data. For technical details and lot-specific validation, contact Ascent Research.
