The IGFBP7 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human hepatic adenocarcinoma cell line SK-HEP-1, engineered for targeted disruption of the IGFBP7 gene. This loss-of-function model enables investigation of tumor suppressor mechanisms and signaling regulation in a liver cancer context without clonal selection bias. The polyclonal format captures heterogeneous gene editing outcomes, providing a physiologically relevant system for dissecting IGFBP7-dependent processes in hepatocellular carcinoma.
SK-HEP-1 cells were originally isolated from the ascites fluid of a patient with liver adenocarcinoma and exhibit a unique endothelial-like phenotype alongside epithelial characteristics. They express endothelial markers such as von Willebrand factor and CD34 and readily form capillary-like tubes in Matrigel, making them an established model for angiogenesis and tumor?Cendothelial interactions. The SK-HEP-1 background thus allows researchers to explore IGFBP7 function not only in tumor cell proliferation and apoptosis but also in vascular mimicry and metastatic dissemination.
IGFBP7 is a secreted tumor suppressor that modulates IGF bioavailability by directly binding IGF1 and IGF2, thereby attenuating IGF1R-mediated AKT and ERK signaling. Concurrently, IGFBP7 activates the TGFBR1/SMAD pathway through interactions with integrins ITGAV/ITGB3 and the receptor ACVRL1, leading to SMAD2/3 phosphorylation and transcriptional induction of the cyclin-dependent kinase inhibitors CDKN1A (p21) and CDKN1B (p27). This dual mechanism promotes cell cycle arrest, apoptosis, and senescence. IGFBP7 expression is transcriptionally regulated by upstream factors including TGFB1, TP53, IL1B, TNF, and HIF1A, integrating stress and cytokine signals. Disruption of IGFBP7 relieves these tumor-suppressive constraints and alters cellular responses to external cues.
In the SK-HEP-1 background, IGFBP7 knockout is expected to enhance proliferation and survival signaling through AKT and ERK, while impairing TGF-??/SMAD-mediated cytostasis. The loss of IGFBP7 may also potentiate pro-angiogenic phenotypes, given the endothelial-like properties of these cells and the gene’s established role in regulating angiogenesis via integrin-mediated adhesion and signaling. This model thus facilitates systematic evaluation of how IGFBP7 deficiency drives hepatocellular carcinoma progression, from dysregulated cell cycle control to enhanced endothelial mimicry and metastatic potential.
This knockout product is suitable for a broad range of applications, including investigation of tumor suppressor networks, drug sensitivity and resistance screening, and modeling of liver cancer metastasis and angiogenesis. Researchers can assess IGFBP7 loss-of-function effects using Western blotting for phospho-AKT and phospho-ERK, RT-qPCR for CDKN1A expression, Annexin V apoptosis assays, MTS cell proliferation assays, Transwell migration assays, tube formation angiogenesis assays, and RNA-seq for transcriptome-wide profiling. The polyclonal knockout population offers a cost-effective and scalable tool for functional genomics studies in hepatocellular carcinoma research. For additional information, please contact Ascent Research.
