The EIF4G3 Knockout 786-O Polyclonal Cells consist of a polyclonal population of the 786-O human renal cell carcinoma line in which the EIF4G3 gene has been disrupted by CRISPR/Cas9-mediated genome editing. This loss-of-function model provides a physiologically relevant tool for studying the scaffolding protein EIF4G3 and its role in cap-dependent translation initiation without the biases inherent to single-cell cloning.
The 786-O cell line is an adherent epithelial model established from a primary clear cell renal cell carcinoma (ccRCC). It carries a naturally occurring truncating mutation in the VHL tumor suppressor gene, which stabilizes hypoxia-inducible factors and drives aberrant angiogenic and proliferative signaling. This genetic background makes 786-O a widely used system for investigating hypoxia-mediated pathways and mTOR signaling in renal cancer.
EIF4G3 functions as the core scaffold of the eIF4F translation initiation complex, bridging the mRNA cap-binding protein eIF4E with the RNA helicase eIF4A and the 40S ribosome-binding factor eIF3. Its assembly is positively regulated by mTORC1, which phosphorylates and inhibits 4E-BP1, releasing eIF4E to interact with EIF4G3. Upstream, PI3K/AKT and MAPK/ERK pathways converge on mTORC1 and MNK kinases to control complex formation. This complex preferentially drives translation of mRNAs with structured 5?? UTRs, including those encoding cyclin D1, c-Myc, VEGF, and Bcl-2.
In the VHL-mutant 786-O context, mTORC1 hyperactivation is common, placing EIF4G3 at the nexus of oncogenic translation and hypoxia-driven tumor biology. Knockout of EIF4G3 allows dissection of cap-dependent translation effects independent of HIF transcriptional outputs, enabling studies of how translation dysregulation contributes to ccRCC proliferation, angiogenesis, and therapeutic resistance. This model is also relevant for breast and prostate cancer research where EIF4G3-dependent translation is implicated.
These cells are suited for a range of assays, including polysome profiling, cap-binding assays, and bicistronic luciferase reporters to quantify cap-dependent translation. Validation can be performed via Western blotting and RT-qPCR, while functional endpoints like proliferation, colony formation, and drug sensitivity assays reveal roles in tumor growth and treatment response. The polyclonal format supports high-throughput screening of translation-targeted compounds and investigations into hypoxia-induced translational reprogramming. For further details, contact Ascent Research.
