The HPCAL1 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human SK-HEP-1 hepatocellular carcinoma cell line, designed to provide a versatile loss-of-function model for the HPCAL1 gene. As a polyclonal pool, this product contains a heterogeneous mixture of cells carrying targeted disruptions in the HPCAL1 locus, allowing researchers to evaluate gene function in a bulk population without clonal selection bias. The CRISPR/Cas9-mediated gene disruption strategy ensures robust knockout across the population while reflecting the natural variability of editing outcomes.
The parental SK-HEP-1 cell line originates from the ascitic fluid of a patient with liver adenocarcinoma and is widely recognized for its highly tumorigenic and metastatic properties in vivo. Notably, SK-HEP-1 retains wild-type TP53 status, which is relevant for studying p53-dependent pathways and drug responses. This background makes the cell line an excellent platform for investigating the molecular mechanisms driving hepatocellular carcinoma progression, invasion, and metastasis.
HPCAL1 encodes hippocalcin-like protein 1, a neuronal calcium sensor family calcium-binding protein that transduces intracellular calcium fluctuations into specific signaling outputs. It physically interacts with the NMDA receptor subunit GRIN1, the metabotropic glutamate receptor GRM1, and voltage-gated calcium channel subunits, positioning it at the interface of calcium influx and downstream pathway activation. HPCAL1 activity is regulated by intracellular calcium levels, cAMP, PKA, and the transcription factor CREB. Downstream, HPCAL1 influences cAMP/PKA signaling effectors, modulates ??-catenin stability via Wnt pathway cross-talk, and affects NMDA receptor function. Key molecular components that intersect with HPCAL1-mediated signaling include calmodulin, CaMKII, calcineurin, PKA, CREB, and ??-catenin.
In the context of SK-HEP-1 hepatocellular carcinoma cells, HPCAL1 is poised to play a critical role in linking calcium signals to malignant phenotypes. Disruption of HPCAL1 in these highly metastatic cells may attenuate calcium-dependent activation of the cAMP/PKA/CREB axis and compromise Wnt/??-catenin signaling, potentially reducing proliferation, migration, and invasive capacity. Therefore, this polyclonal knockout model offers a powerful system to dissect the contributions of calcium-binding proteins to liver cancer aggressiveness. Additionally, the TP53 wild-type background permits examination of p53-related drug sensitivities, enabling the evaluation of therapeutic vulnerabilities in a genetically defined context.
The HPCAL1 Knockout SK-HEP-1 Polyclonal Cells are suitable for a broad array of research applications, including hepatocellular carcinoma studies, intracellular calcium signaling analysis, metastasis mechanism investigation, and drug sensitivity testing. Knockout efficiency can be confirmed by Western blotting, RT-qPCR, or RNA-seq, while functional consequences are assessed via migration/invasion assays, colony formation assays, and calcium imaging. For pathway-focused readouts, researchers can employ phospho-PKA substrate antibody arrays to monitor PKA activity or ??-catenin reporter assays to quantify Wnt/??-catenin signaling outputs. For further information or to discuss custom gene-editing projects, please contact Ascent Research.
