The ITPR1 Knockout SK-HEP-1 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout population derived from the SK-HEP-1 hepatocellular carcinoma cell line. This pooled cell population carries targeted disruption of the ITPR1 gene, providing a loss-of-function model for dissecting IP3 receptor-mediated calcium signaling. The polyclonal format preserves genetic heterogeneity, making it suitable for robust functional analyses without the biases of single-cell cloning.
SK-HEP-1 is an immortalized human liver cancer cell line isolated from ascites of a patient with adenocarcinoma. Despite an endothelial-like morphology, it serves as a well-characterized model for hepatocellular carcinoma and hepatic endothelial physiology. The line retains critical oncogenic signaling circuits, including calcium-regulated pathways that influence proliferation and survival, thus offering a relevant host for ITPR1 functional studies.
ITPR1 encodes the IP3-gated endoplasmic reticulum calcium release channel. Following IP3 production by PLC downstream of GPCRs or receptor tyrosine kinases, ITPR1 mediates intracellular Ca2+ mobilization. This calcium signal activates calcineurin, which dephosphorylates NFAT transcription factors, and stimulates CaMK, PKC, and CREB. ITPR1 also interacts with IRAG, Homer, and Bcl-2 family proteins to link calcium release to ER-mitochondrial communication, apoptosis, and autophagy. Channel activity is fine-tuned by kinases such as PKA, PKC, and CaMKII, positioning ITPR1 as a key integrator of calcium-dependent cell fate decisions.
In the SK-HEP-1 liver cancer context, disruption of ITPR1 interrupts IP3-driven calcium oscillations that drive oncogenic proliferation and survival. Loss of ITPR1 function impairs calcineurin/NFAT and CaMK/CREB signaling, potentially reducing tumorigenic potential and sensitizing cells to apoptotic or autophagic stimuli. This knockout model thus permits systematic evaluation of calcium-dependent pathways in hepatocellular carcinoma, including their crosstalk with MAPK and store-operated calcium entry mechanisms.
Applications include calcium signaling studies using Fluo-4 AM imaging, proliferation (MTT), apoptosis (Annexin V), and autophagy flux (LC3-II) assays. The cells are suited for screening calcium channel modulators, examining ITPR1 role in spinocerebellar ataxia type 15/16, and profiling phospho-signaling arrays. The knockout population also enables migration assays and drug response testing. For further information, please contact Ascent Research.
