The ATF3 Knockout HT-1080 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from the well-characterized human fibrosarcoma cell line HT-1080. This product features targeted disruption of the ATF3 gene, resulting in a stable loss-of-function model for investigating ATF3-mediated processes. The knockout is generated via CRISPR/Cas9 genome editing without further specification of editing outcome, and the cell line is provided as a validated, ready-to-use culture system for advanced cellular and molecular assays.
The parental HT-1080 line originates from a fibrosarcoma biopsy taken from a 35-year-old male. It exhibits a near-diploid karyotype with multiple chromosomal aberrations and harbors an activating N-RAS Q61K mutation along with deletion or inactivation of p53. This genetic background drives a highly invasive, anchorage-independent growth phenotype, making HT-1080 cells a standard model for studying cancer cell invasion, metastasis, and the tumor microenvironment.
ATF3 is a member of the ATF/CREB family of stress-inducible transcription factors. It is rapidly upregulated by diverse stimuli, including ER stress, oxidative stress, DNA damage, and inflammatory cytokines such as TNF-??, TGF-??, and IL-1??, primarily through JNK and p38 MAPK pathways and ATF4. Once activated, ATF3 can function as a transcriptional activator or repressor depending on its dimerization partners, which include c-Jun, JunB, JunD, ATF2, and interacts with p53, Smad3, NF-??B p65, HDAC1, and PCAF. ATF3 regulates target genes including CHOP (DDIT3), GADD45A, CCND1, MMP-2, MMP-9, Bax, Bcl-2, p21 (CDKN1A), and ID1, integrating MAPK, JNK/p38, TGF-??, NF-??B, and p53 signaling and the unfolded protein response.
Within HT-1080 cells, ATF3 knockout is particularly instructive due to the active N-RAS oncogene and deficient p53 tumor suppressor. ATF3 can influence apoptosis, cell cycle progression, and invasive capacity; its disruption may rebalance pro-apoptotic versus pro-survival signals and alter the expression of matrix metalloproteinases such as MMP-2 and MMP-9, directly impacting motility. This genetically defined model allows researchers to dissect the context-dependent roles of ATF3 in mesenchymal tumorigenesis and stress adaptation.
This knockout cell line supports a wide range of experimental applications, including the analysis of cellular stress responses, apoptosis and cell cycle control, tumor cell invasion and metastasis, and evaluation of drug sensitivity and resistance. Typical assays include western blotting for ATF3 and downstream targets, RT-qPCR profiling of ATF3-regulated genes, Annexin V apoptosis assays and caspase activity measurements, flow cytometric cell cycle analysis, Transwell migration and invasion assays, ChIP-qPCR for ATF3 promoter binding, RNA-seq transcriptome profiling, and reporter assays. The model is relevant to research in oncology, inflammatory diseases, metabolic syndrome, neurodegeneration, and ischemia-reperfusion injury. For further information or to request a quote, please contact Ascent Research.
