KIDINS220 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population from the SK-HEP-1 hepatocellular carcinoma line with targeted KIDINS220 gene disruption. This heterogeneous pool provides a loss-of-function model for studying KIDINS220-dependent receptor signaling. The polyclonal nature captures diverse editing events, permitting robust phenotypic assessment without clonal artifacts. Researchers can use these cells to interrogate KIDINS220-mediated processes in a liver cancer epithelial context that also exhibits endothelial-like properties.
The parental SK-HEP-1 line was derived from the ascitic fluid of a 52-year-old male with liver adenocarcinoma and is widely used as a hepatocellular carcinoma model. Notably, SK-HEP-1 cells display endothelial-like characteristics, including expression of vascular markers, rendering them valuable for studies of tumor plasticity, angiogenesis-related signaling, and transdifferentiation. Their dual epithelial-endothelial identity enables dissection of KIDINS220 functions in cell-autonomous signaling and microenvironmental interactions relevant to hepatocellular carcinoma progression.
KIDINS220 (ARMS) is a scaffold protein that couples activated TrkA/TrkB (by NGF/BDNF) and EphA (by Ephrin-A) receptors to intracellular signaling cascades. It recruits adaptors SHC and GRB2 to activate the MAPK/ERK cascade and PI3K/AKT pathway, and directly binds PLC??1 to trigger calcium/PKC signaling. Downstream effectors ERK, AKT, and PLC?? regulate transcription factors such as CREB, c-Fos, and NF-??B, thereby controlling gene programs for survival, differentiation, and migration.
In SK-HEP-1 cells, KIDINS220 knockout disrupts the scaffold required for Trk and Eph receptor signal transduction, likely impairing MAPK/ERK and PI3K/AKT activation. Since these pathways drive liver cancer proliferation, survival, and invasion, KIDINS220 loss is anticipated to diminish neurotrophin and ephrin responses. The endothelial-like features of SK-HEP-1 further position this model to explore KIDINS220-dependent crosstalk between tumor signaling and vascular mimicry or metastatic dissemination.
This knockout model enables dissection of neurotrophin and ephrin signaling via western blotting for KIDINS220 and flow cytometry for phospho-ERK/AKT. Transwell assays assess migration and invasion, while RT-qPCR quantifies downstream targets such as c-Fos and CREB. Immunofluorescence and co-immunoprecipitation of TrkA?CKIDINS220 complexes validate scaffold-receptor interactions. Cell viability and apoptosis assays measure responses to Trk inhibitors in drug screening. For further technical details, please contact Ascent Research.
