The JPH2 Knockout NCI-H1975 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal cell population derived from the NCI-H1975 human lung adenocarcinoma epithelial cell line, engineered to disrupt the JPH2 gene. This loss-of-function model provides a heterogeneous knockout pool that mirrors population-level gene disruption, making it well-suited for functional studies where clonal homogeneity is not required. The polyclonal format facilitates robust assessment of JPH2-dependent phenotypes in a cancer-relevant background without the constraints of single-cell cloning.
The NCI-H1975 host cell line originates from a female patient with lung adenocarcinoma and harbors wild-type EGFR, rendering the cells sensitive to EGFR tyrosine kinase inhibitors. This line is broadly employed as a model for non-small cell lung cancer (NSCLC), particularly for investigating signaling pathways that intersect with EGFR biology. The epithelial morphology and well-characterized mutational landscape make NCI-H1975 a reliable platform for studying oncogenic processes and therapeutic responses. In combination with JPH2 disruption, the line offers a unique context to explore cross-talk between calcium-handling proteins and cancer cell signaling.
JPH2 encodes junctophilin-2, a membrane-tethering protein that anchors the plasma membrane to the endoplasmic/sarcoplasmic reticulum and is critical for organizing junctional membrane complexes in excitable cells. JPH2 facilitates calcium-induced calcium release by bridging Cav1.2 channels and RyR2 release channels. It interacts with caveolin-3, TRPC3, and calmodulin, and its expression is regulated by MEF2, SRF, and mechanical stress. Knockout disrupts calcium homeostasis, impairing excitation-contraction coupling and altering calcineurin/NFAT signaling, with downstream effects on calcium-handling proteins such as SERCA2a and calsequestrin.
In the NCI-H1975 background, JPH2 knockout provides a tool to dissect calcium-mediated signaling in epithelial cancer cells where junctophilin-2 is not dominantly expressed. This model enables investigation of off-target effects in lung cancer, as JPH2 disruption may modulate calcium-dependent proliferation, migration, and drug sensitivity. Because NCI-H1975 cells are sensitive to EGFR inhibitors, the knockout line facilitates studies evaluating interplay between calcium handling and EGFR-driven oncogenic pathways. Moreover, it serves as a surrogate system for evaluating compounds targeting JPH2-associated functions, including those for hypertrophic cardiomyopathy.
Researchers can employ the JPH2 Knockout NCI-H1975 Polyclonal Cells in a range of experimental workflows, including calcium imaging to monitor intracellular calcium dynamics, co-immunoprecipitation to probe protein interactions, and western blotting or RT-qPCR for expression analysis. The polyclonal population is well-suited for cell proliferation assays and drug sensitivity screens under varied calcium conditions. Additionally, this model supports functional genomics studies and drug screening efforts for cardiomyopathies, leveraging its genetic disruption of a central calcium-handling node. For further technical specifications, please contact Ascent Research.
