The IGF1R Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the 786-O human clear cell renal cell carcinoma line, harboring a targeted disruption of the IGF1R gene. This loss-of-function model eliminates expression of the insulin-like growth factor 1 receptor, providing a genetically defined system to investigate IGF1R-dependent signaling in renal cancer.
The 786-O cell line was established from a primary clear cell renal adenocarcinoma of a 58-year-old male and serves as a widely used epithelial model for renal cell carcinoma (RCC). These cells carry the characteristic VHL gene inactivation found in the majority of sporadic ccRCC cases and display typical tumorigenic properties, including colony formation in soft agar and tumor growth in xenograft models. Their well-documented genetic and phenotypic features make them an appropriate host for studying oncogenic pathways relevant to kidney cancer.
IGF1R encodes a receptor tyrosine kinase that is activated by its cognate ligands IGF1 and IGF2, as well as by insulin at supraphysiological concentrations. Ligand binding induces receptor autophosphorylation and recruitment of adaptor proteins IRS1 and SHC, which initiate two major signaling branches: the IRS1?CPI3K?CAKT?CmTOR?CS6K cascade and the SHC?CGRB2?CSOS?CRAS?CRAF?CMEK?CERK1/2 pathway. In addition, IGF1R can signal through JAK/STAT proteins (STAT1/3/5) to regulate transcription. The receptor??s activity is modulated by upstream regulators including insulin-like growth factor-binding proteins (IGFBPs) and growth hormone, and it interacts with integrins, EGFR, and E-cadherin to coordinate cellular responses. Downstream, IGF1R promotes proliferation through cyclin D1, survival via phosphorylation of BAD and FOXO factors, and protein synthesis through mTOR/S6K.
In the context of 786-O cells, the IGF1R knockout model offers a precise tool to examine the receptor??s role in ccRCC pathophysiology. IGF1R signaling has been implicated in renal tumor cell growth, survival, and metastatic behavior. By comparing parental and knockout populations, researchers can assess the reliance of 786-O cells on IGF1R for sustained proliferation, migration, and resistance to apoptosis, as well as identify compensatory pathways that may emerge. This isogenic system also facilitates the dissection of IGF1R crosstalk with other oncogenic drivers, such as mutated VHL?CHIF axis, to understand tumor maintenance mechanisms.
Researchers can employ this polyclonal knockout product in a variety of experimental workflows, including phospho-signaling analysis by western blotting, flow cytometric assessment of cell cycle and apoptosis, RT-qPCR or RNA-seq transcriptomics, and functional assays for migration and invasion. It is particularly valuable for drug target validation and for investigating resistance mechanisms to agents such as mTOR inhibitors and tyrosine kinase inhibitors in RCC. Applications also extend to metabolic studies of IGF1R-regulated glycolysis and lipid metabolism. For detailed technical specifications or to inquire about custom applications, please contact Ascent Research.
