ATIC Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the SK-HEP-1 human hepatocellular carcinoma cell line, featuring targeted disruption of the ATIC gene. ATIC encodes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase, and the polyclonal format provides a heterogeneous loss-of-function model suitable for studying purine metabolism and metabolic stress without monoclonal isolation.
The parental SK-HEP-1 line is a hepatic adenocarcinoma model from ascites of a liver cancer patient, displaying adherent epithelial morphology. It is extensively used in hepatocellular carcinoma research for investigating metabolic reprogramming, drug resistance, and oncogenic signaling, making it an appropriate background to examine purine biosynthesis dependencies in proliferating cancer cells.
ATIC catalyzes the final two steps in de novo purine biosynthesis: AICAR transformylase and IMP cyclohydrolase activities. The protein functions within the purinosome complex alongside GART, PAICS, and ADSL, and its expression is transcriptionally regulated by MYC and E2F1 downstream of mTORC1 and folate sensing. ATIC disruption halts conversion of AICAR to FAICAR and IMP, leading to AICAR accumulation and purine nucleotide depletion (IMP, AMP, GMP). Accumulated AICAR activates AMPK through ??-subunit binding, promoting phosphorylation of ACC and TSC2, thereby triggering metabolic checkpoint signaling and cell cycle arrest.
In SK-HEP-1 hepatocellular carcinoma cells, ATIC knockout induces metabolic stress via AICAR-driven AMPK activation and purine scarcity. Given the high nucleotide demand of liver cancer cells, this model enables dissection of AMPK-mediated growth suppression and exploration of synthetic lethal interactions. It also serves as a tool for studying AICA-ribosiduria and related inborn errors of purine metabolism.
Research applications include cancer metabolism studies, AMPK signaling investigation, and drug target validation in purine biosynthesis. Assays such as western blotting for ATIC and phospho-AMPK, LC-MS quantitation of AICAR and purine nucleotides, flow cytometry for cell cycle, colony formation, and AMPK kinase assays are directly applicable. This product accelerates mechanistic and translational research into purine-dependent malignancies. For further information, contact Ascent Research.
