The ATF3 Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the A-549 human lung adenocarcinoma cell line, carrying a targeted disruption of the ATF3 gene. This heterogeneous pool provides a robust loss-of-function model to study ATF3-dependent signaling networks and stress responses in a physiologically relevant lung cancer background.
The A-549 cell line is an adherent epithelial model isolated from human lung adenocarcinoma tissue. It harbors a KRAS G12S mutation, a prevalent oncogenic driver in non-small cell lung cancer (NSCLC), and is widely utilized for respiratory research, drug response profiling, and investigation of oncogenic signaling pathways, including MAPK and PI3K cascades.
ATF3 is a stress-inducible transcription factor of the ATF/CREB family, rapidly activated by diverse stimuli including DNA damage, oxidative stress, ER stress, and hypoxia. Upstream kinases JNK (MAPK8), p38 (MAPK14), and ERK1 (MAPK3), along with p53 and NF-??B, phosphorylate and induce ATF3, which then regulates gene expression programs for apoptosis, cell cycle arrest, and inflammation. ATF3 interacts with JUN, JUNB, JUND, ATF2, TP53, SMAD3, HDAC1, and RELA to modulate transcription of targets such as cyclin D1, p21, PUMA, HSP70, CHOP, and GADD34, thereby integrating signals from MAPK, p53, NF-??B, and TGF-?? pathways.
In KRAS-mutant A-549 cells, ATF3 knockout disrupts stress-responsive transcriptional programs, altering the balance between pro-apoptotic and pro-survival signals, cell cycle progression, and inflammatory cytokine production. Given ATF3’s context-dependent dual role as a tumor suppressor or oncogene, this model enables precise analysis of its function in NSCLC progression, including effects on apoptosis, cell cycle arrest, and inflammatory signaling. It is particularly valuable for studying ATF3-mediated chemoresistance to agents such as cisplatin and erlotinib, and for dissecting crosstalk between MAPK and p53 pathways.
This polyclonal knockout pool supports functional genomics applications including RNA-seq transcriptome profiling, RT-qPCR and western blotting for target validation, apoptosis and cell cycle assays, proliferation, wound healing, transwell invasion, luciferase reporter assays for ATF-binding element activity, phospho-kinase arrays, and drug sensitivity testing. It enables comprehensive investigation of ATF3 in lung adenocarcinoma, stress response, and metastasis. For further information, contact Ascent Research.
