The HLTF Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from human SK-HEP-1 liver adenocarcinoma epithelial cells. This heterogeneous model features targeted disruption of HLTF across the population, providing a versatile tool for loss-of-function studies. The polyclonal format preserves genetic variability, enabling robust population-level analyses.
The SK-HEP-1 parental line originates from a liver adenocarcinoma and serves as a widely used hepatocellular carcinoma (HCC) model. These adherent epithelial cells support reproducible genetic manipulation and are routinely employed to study HCC biology, including tumor progression and drug responses, offering a well-characterized platform for cancer gene research.
HLTF is a dual-function DNA helicase and E3 ubiquitin ligase critical for the DNA damage response. It promotes PCNA polyubiquitination together with RAD18 and UBE2B, facilitating translesion synthesis and homologous recombination. Upstream, ATM and ATR activate HLTF upon genotoxic stress, while E2F transcription factors regulate its expression. HLTF interacts with RAD51 and FANCD2 to stabilize replication forks and remodels chromatin at damage sites. Functional links to BRCA1 further connect HLTF to homologous recombination fidelity. In Wnt signaling, HLTF loss elevates ??-catenin stability, and its tumor-suppressive functions are mediated partly through p53-dependent pathways.
In hepatocellular carcinoma, HLTF deficiency is linked to tumor initiation and genomic instability. This SK-HEP-1 knockout model allows dissection of HLTF??s roles in DNA repair, chromatin remodeling, and Wnt/??-catenin signaling within a hepatic context. Given the high prevalence of p53 and ??-catenin mutations in HCC, this model is especially relevant for studying how HLTF loss cooperates with these oncogenic alterations to promote tumorigenesis. Consequently, it is valuable for investigating how HLTF loss alters chemotherapeutic responses and oncogenic signaling.
Applications include Western blotting and RT-qPCR for confirming HLTF disruption and measuring effectors like PCNA, RAD51, and ??-catenin. RNA-seq enables transcriptome-wide analysis, while ChIP-qPCR assesses chromatin occupancy changes. Immunofluorescence for ??H2AX foci and flow cytometry for cell cycle and apoptosis provide functional repair and survival readouts. Drug sensitivity assays with genotoxic agents (e.g., cisplatin, PARP inhibitors) probe resistance mechanisms. For additional details, contact Ascent Research.
