The EIF4G3 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the HGC-27 human gastric carcinoma cell line, with targeted disruption of the EIF4G3 gene. This model provides a loss-of-function system to study the role of the eIF4G3 scaffold protein in cap-dependent translation initiation within a gastric cancer context. The polyclonal format maintains genetic diversity, enabling population-level analyses of gene disruption effects.
HGC-27 is an epithelial cell line isolated from a lymph node metastasis of a poorly differentiated gastric adenocarcinoma. It serves as a widely used model for gastric cancer research, recapitulating aggressive tumor features including aberrant growth signaling and invasive behavior. The cell line offers a relevant background for investigating translational control mechanisms that contribute to gastric tumorigenesis.
EIF4G3 serves as a central scaffold in the eIF4F complex, linking the cap-binding protein eIF4E with the helicase eIF4A and recruiting the 40S ribosomal subunit via eIF3 to facilitate cap-dependent translation. Its activity is governed by the mTOR signaling pathway: mTOR-mediated phosphorylation of 4E-BP1 releases eIF4E to associate with eIF4G, while upstream activators including PI3K, AKT, PDK1, and growth factors (EGF, IGF) converge on mTORC1. EIF4G3 also interacts with PABPC1, Mnk1, and the regulatory factor PDCD4. Downstream, the eIF4F complex promotes synthesis of oncogenic proteins such as cyclin D1, MYC, BCL2, VEGF, and MMPs, which drive proliferation, survival, and metastasis. In gastric cancer, sustained mTOR pathway activity elevates EIF4G3-dependent translation, supporting malignant progression.
Knockout of EIF4G3 in HGC-27 cells abrogates eIF4F complex assembly, effectively uncoupling mTOR-driven signals from the translational apparatus. This is particularly pertinent given the frequent hyperactivation of the PI3K/AKT/mTOR pathway in gastric adenocarcinoma, which enhances expression of multiple oncogenic factors. By removing the scaffold, researchers can delineate the specific contribution of cap-dependent translation to gastric cancer phenotypes, investigate compensatory mechanisms, and evaluate synthetic lethality. The polyclonal knockout approach mirrors the heterogeneous responses seen in tumor populations, offering a more physiologically relevant model than monoclonal derivatives.
This knockout product is suitable for diverse experimental workflows, including polysome profiling and RNA immunoprecipitation to assess translation initiation complexes, cap-binding assays to measure eIF4F activity, and proliferation or migration assays to link EIF4G3 function to gastric cancer cell behavior. It facilitates drug sensitivity studies using mTOR inhibitors (e.g., rapamycin) and global analyses of translational efficiency via RNA-seq or ribosome profiling. The model also supports biomarker discovery and therapeutic targeting of the translation machinery. For additional information, please contact Ascent Research.
