The IGF2 Knockout LoVo Polyclonal Cells product comprises a heterogeneous polyclonal population of the LoVo colorectal adenocarcinoma cell line engineered via CRISPR/Cas9-mediated gene disruption of the human insulin-like growth factor 2 (IGF2) locus. This polyclonal knockout pool is designed to generate loss-of-function models for functional genomics studies, without clonal isolation or biallelic knockout selection. The product format provides a versatile reagent for investigating IGF2-dependent phenotypes in a cancer-relevant cellular context.
The parental LoVo cell line is a well-characterized epithelial model derived from a metastatic lymph node of a 56-year-old male with colorectal adenocarcinoma. LoVo cells retain key genetic features of metastatic colorectal cancer, including aberrant activation of growth factor signaling cascades, making them a robust host for studying genes implicated in tumor progression and dissemination. Their metastatic origin and established use in xenograft models provide a clinically relevant platform for evaluating oncogenic mechanisms.
IGF2 encodes a potent fetal mitogen that is frequently overexpressed in colorectal and other cancers, where it acts in an autocrine/paracrine manner to drive proliferation, survival, and protein synthesis. IGF2 binds and activates the insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor isoform A (INSR-A), recruiting insulin receptor substrate 1 (IRS1) and initiating downstream signaling through the PI3K/AKT and RAS/RAF/MEK/ERK cascades. AKT phosphorylates substrates such as FOXO, GSK3, and S6K, while ERK promotes transcriptional programs involving cyclin D1 and BCL-2. Upstream regulation of IGF2 involves complex imprinting control via the H19/IGF2 locus, with DNA methylation and binding of CTCF, as well as transcription factors PLAG1 and HMGA2. The signaling network is modulated by a family of IGF-binding proteins (IGFBP1?6), which fine-tune ligand bioavailability.
In the LoVo metastatic colorectal cancer model, autocrine/paracrine IGF2 signaling contributes to sustained activation of survival and mitogenic pathways, supporting uncontrolled growth and metastatic potential. Disruption of IGF2 in this polyclonal knockout population provides a direct means to interrogate its role in maintaining transformed phenotypes, including anchorage-independent growth, migration, and invasion. The model is particularly suited for dissecting IGF1R/INSR-dependent and -independent mechanisms, as well as for studying the interplay between the IGF system and other oncogenic drivers commonly altered in colorectal carcinoma.
These polyclonal knockout cells are an ideal tool for functional analysis of IGF2 in colorectal cancer biology, including proliferation and metastasis assays such as MTT, colony formation, and Boyden chamber migration/invasion. They can be employed to assess signaling downstream of IGF2 using western blotting for phospho-AKT, phospho-ERK, and their targets, or phospho-signaling antibody arrays. Additionally, the model supports imprinted gene regulation studies, testing of IGF1R-targeted therapeutics (e.g., small-molecule inhibitors), and drug resistance research. Transcriptomic analysis via RNA-seq can reveal IGF2-dependent gene expression programs. For further technical details or customized applications, please contact Ascent Research.
