The GPRC5C Knockout SK-HEP-1 Polyclonal Cells product comprises a polyclonal population of SK-HEP-1 cells engineered via CRISPR/Cas9 to disrupt the GPRC5C gene, establishing a loss-of-function model for the orphan G protein-coupled receptor GPRC5C. This targeted gene disruption impairs receptor function, enabling researchers to dissect its putative tumor-suppressive roles in a hepatocellular carcinoma context. The polyclonal format captures a spectrum of editing events, suitable for pooled functional analyses without clonal selection bias.
SK-HEP-1 is a human liver adenocarcinoma-derived cell line that retains hepatic parenchymal characteristics and is broadly used as a hepatocellular carcinoma (HCC) model. Originally established from a patient’s hepatic adenocarcinoma, this adherent epithelial line provides a physiologically relevant system for investigating HCC biology, including tumor proliferation, metastatic dissemination, and therapeutic response. Its widespread adoption underpins studies of molecular drivers in hepatocarcinogenesis.
GPRC5C encodes an orphan class C GPCR implicated as a potential tumor suppressor through modulation of key oncogenic signaling cascades. At the plasma membrane, it couples to heterotrimeric G proteins such as GNAQ and GNA11, and its expression is controlled by upstream factors including transcription factors, DNA methylation, and histone modifications. Downstream, GPRC5C intersects with the MAPK cascade via MAP2K1 and MAPK1 (ERK1/2) and the PI3K-AKT pathway via AKT1, while also influencing Wnt/??-catenin signaling through CTNNB1. Receptor activity is further tuned by interacting partners ??-arrestins and RGS proteins, which regulate signal kinetics. Disruption of GPRC5C is expected to release inhibitory constraints on these pathways, leading to enhanced phosphorylation of ERK1/2 and AKT and increased ??-catenin transcriptional activity.
In the HCC context, loss of GPRC5C-mediated tumor suppression promotes aggressive malignant phenotypes, making this polyclonal knockout model valuable for deciphering GPRC5C’s role in liver cancer. The model aids in elucidating how orphan receptor dysfunction accelerates MAPK and PI3K-AKT pathway hyperactivation, driving uncontrolled proliferation, migration, and survival. Additionally, because GPRC5C is also implicated in colorectal and gastric cancers, these cells support comparative oncology studies beyond HCC.
Researchers can apply these cells in diverse functional assays: proliferation (MTT, BrdU), migration/invasion (Transwell), and apoptosis (Annexin V) to quantify oncogenic behaviors; western blotting and phospho-ERK/AKT analysis to monitor signaling node activation; and RT-qPCR or RNA-seq to capture transcriptome-wide changes. Co-immunoprecipitation and luciferase-based reporter assays (e.g., ??-catenin/TCF reporters) facilitate exploration of protein interactions and pathway crosstalk. The model is also suited for screening GPCR ligands that may reactivate GPRC5C signaling. For detailed technical specifications or experimental support, please contact Ascent Research.
