The EIF2AK4 Knockout HGC-27 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population engineered to disrupt the EIF2AK4 gene in the HGC-27 human gastric cancer background. This loss-of-function model is provided as a heterogeneous pool of edited cells, enabling researchers to investigate the integrated stress response and amino acid sensing pathways without clonal artifacts. The target gene, EIF2AK4, encodes the kinase GCN2, a central sensor of nutrient deprivation and stress, making this product a valuable tool for studying cellular adaptation and survival mechanisms in gastric carcinoma.
HGC-27 is an epithelial cell line derived from the lymph node metastasis of a gastric carcinoma patient, and it is widely employed in gastric cancer research to model tumor biology, metastasis, and drug responses. These cells retain key characteristics of gastric cancer, including relevant oncogenic signaling networks and metabolic dependencies, providing a physiologically relevant host for interrogating gene function. The polyclonal knockout population captures the heterogeneity of CRISPR-induced edits, reflecting the complexity of gene disruption in a cancer cell context, which is particularly useful for studying tumor cell behavior and clonal evolution.
EIF2AK4 (GCN2) functions as a serine/threonine kinase that is activated by amino acid deprivation, uncharged tRNA accumulation, UV radiation, and proteasome inhibition. Upon activation, GCN2 phosphorylates the ?? subunit of eukaryotic translation initiation factor 2 (eIF2??), leading to global translation attenuation while selectively promoting the translation of ATF4. The GCN2?CeIF2???CATF4 axis constitutes the core of the integrated stress response, with ATF4 subsequently inducing downstream targets such as CHOP, ASNS, and other genes involved in amino acid metabolism and redox homeostasis. GCN2 interacts with GCN1, the ribosome, and IMPACT, forming a regulatory hub that coordinates stress signaling with mTOR and autophagy pathways.
In the HGC-27 gastric cancer context, disruption of EIF2AK4 offers a powerful model to dissect how cancer cells sense and respond to nutrient fluctuations in the tumor microenvironment. Gastric tumors often encounter amino acid scarcity and metabolic stress; thus, GCN2-dependent signaling is implicated in tumor survival, drug resistance, and the regulation of autophagy. This knockout model enables the study of how loss of this sensor alters cancer cell proliferation, invasion, and sensitivity to chemotherapeutic agents or targeted therapies, providing insights into potential therapeutic vulnerabilities.
This polyclonal knockout product is suited for a broad range of experimental applications, including amino acid deprivation assays, phospho-signaling analysis (e.g., western blotting for phosphorylated eIF2?? and ATF4 levels), RT-qPCR profiling of stress-responsive genes, metabolic flux analyses, and drug sensitivity screens. It is an ideal system for investigating the crosstalk between the integrated stress response and oncogenic pathways in gastric cancer. For additional details on characterization, quality control, or customized applications, please contact Ascent Research.
