The IGF2 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the IGF2 gene in the HCT 116 colorectal carcinoma cell line. This mixed polyclonal pool contains heterogeneous gene disruptions, avoiding clonal artifacts and suitable for population-level functional analyses. The model supports investigations into IGF2-dependent phenotypes in cancer biology and signal transduction.
HCT 116 is a human colon adenocarcinoma epithelial cell line harboring a KRAS G13D mutation, stable ??-catenin expression, and microsatellite instability (MSI) from mismatch repair deficiency. This MSI-positive, KRAS-mutant background is widely used to study colorectal tumorigenesis and oncogenic signaling, particularly the RAS/RAF/ERK and PI3K/AKT pathways.
IGF2 (insulin-like growth factor 2) is a paternally expressed imprinted fetal growth factor that promotes cell proliferation and survival. Its transcription is regulated by the H19/IGF2 imprinting control region and factors such as Wnt/??-catenin and SP1. Secreted IGF2 binds IGF1R and IR-A, activating IRS1-mediated PI3K/AKT and RAS/RAF/ERK signaling cascades, leading to phosphorylation of AKT and ERK1/2. Downstream, these pathways regulate MYC, CCND1, and BCL2, among other effectors, while bioavailability is modulated by IGFBP3 and IGFBP5.
In HCT 116 cells, IGF2 acts as an autocrine growth factor, sustaining PI3K/AKT and MAPK/ERK activity. Knockout disrupts this loop, reducing phospho-AKT and phospho-ERK levels, impairing proliferation, and promoting apoptosis. Combined with the MSI and KRAS G13D background, this model allows dissection of IGF2??s contribution to colorectal cancer cell fitness and provides a platform for studying genotype-specific signaling dependencies.
Applications include mechanistic studies of colorectal cancer progression, cancer stem cell biology, and drug resistance (e.g., 5-FU sensitivity). The cells are suitable for functional assays such as western blotting for phosphorylated AKT/ERK, colony formation, caspase 3/7 apoptosis detection, MTS viability, RT-qPCR, and RNA-seq. They also support genomic imprinting research at the H19/IGF2 locus. For additional details, contact Ascent Research.
