The IGF2R Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HCT 116 human colorectal carcinoma cell line. This product provides a targeted disruption of the IGF2R gene, which encodes the insulin-like growth factor 2 receptor, resulting in loss of IGF2R protein expression and functional activity. The polyclonal format comprises a heterogeneous mixture of independently edited cells, offering a robust loss-of-function model that avoids the potential confounding effects of clonal selection and adaptation often associated with monoclonal lines.
The host HCT 116 cell line is a widely utilized epithelial model of colorectal carcinoma, originally established from a primary colorectal adenocarcinoma. This mismatch repair-deficient line exhibits microsatellite instability-high (MSI-H) and carries a heterozygous KRAS G13D mutation, making it an appropriate system for studying tumor suppressor pathways and oncogenic signaling in a genetic context relevant to many human colorectal cancers. The line??s well-characterized growth properties and molecular profile support reliable experimental reproducibility.
IGF2R functions as a potent tumor suppressor by binding and internalizing its primary ligand, insulin-like growth factor 2 (IGF2), thereby targeting the mitogen for lysosomal degradation. This clearance mechanism suppresses IGF1R-mediated signaling, evidenced by diminished phosphorylation of downstream kinases Akt and MAPK. Additionally, IGF2R acts as the cation-independent mannose-6-phosphate receptor, directing mannose-6-phosphate-tagged lysosomal enzymes such as cathepsins to lysosomes, and facilitates activation of latent TGF-beta1 through proteolytic processing, which in turn triggers Smad-dependent growth inhibition. Expression of IGF2R is transcriptionally activated by TP53, but is frequently silenced in cancers via promoter hypermethylation, and can be regulated by microRNAs like miR-615-3p. Key interacting partners include retinoic acid and uPAR, which modulate receptor trafficking and function.
In the HCT 116 background, CRISPR/Cas9-mediated disruption of IGF2R creates a valuable isogenic model to delineate its tumor-suppressive role amidst coexisting oncogenic KRAS signaling and mismatch repair defects. By eliminating IGF2R, researchers can interrogate how unchecked IGF2 bioavailability and persistent IGF1R/Akt/MAPK pathway activity drive enhanced proliferation, apoptosis resistance, and migratory capacity. This model also permits examination of compromised TGF-beta activation and lysosomal enzyme sorting, revealing contributions to malignant progression and altered therapeutic vulnerabilities.
This polyclonal knockout cell pool is tailored for diverse investigations, including dissection of the IGF2/IGF1R axis in colorectal cancer tumor suppression, TGF-beta activation mechanisms, and lysosomal enzyme trafficking studies. Representative assays include phospho-IGF1R western blotting, IGF2 internalization assays, cell proliferation and apoptosis analyses, and transwell migration assays. The model further supports cancer metabolism and drug resistance studies, where the effect of IGF2R loss on chemosensitivity can be assessed. For additional information, validation data, or custom applications, please contact Ascent Research.
