The HOMER2 Knockout NCI-H1975 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the HOMER2 gene in the human lung adenocarcinoma NCI-H1975 cell line. This loss-of-function model eliminates expression of the HOMER2 scaffold protein, a critical adaptor in multiple signaling cascades. The polyclonal nature provides a heterogeneous genetic background representative of diverse cellular responses, suitable for robust functional analyses without clonal variation. These polyclonal knockout cells offer a reliable tool for investigating HOMER2-dependent pathways in a cancer-relevant context.
The host cell line, NCI-H1975, is a well-characterized non-small cell lung cancer model derived from lung adenocarcinoma and harbors the EGFR L858R/T790M double mutation. This mutation confers sensitivity to first- and third-generation tyrosine kinase inhibitors, making it invaluable for studying EGFR-driven oncogenic signaling and therapeutic resistance. NCI-H1975 retains key features of tumorigenic pathways and is widely used to dissect mechanisms of proliferation, migration, and drug response, providing a clinically relevant backdrop for HOMER2 studies.
HOMER2 is a scaffold protein that physically couples group I metabotropic glutamate receptors (GRM1, GRM5) to inositol 1,4,5-trisphosphate receptors (ITPR1), thereby regulating calcium release. It functions downstream of the TCR/CD3 complex and Ca2+/calmodulin, bridging receptor activation to downstream effectors including NFATC1, CREB, MAPK1/ERK2, and PLCB1. HOMER2 interacts with SHANK and PLCB, contributing to the assembly of signaling complexes such as GRM1-HOMER2-ITPR1-Ca2+ and TCR-CD3-HOMER2-NFATC1. Through these interactions, it influences calcium signaling, MAPK/ERK pathway activation, and transcriptional responses.
In NCI-H1975 lung adenocarcinoma cells with EGFR mutations, HOMER2 knockout provides a means to explore crosstalk between GPCR scaffolding and oncogenic kinase signaling. Disruption of HOMER2 may alter calcium homeostasis, NFAT-dependent transcription, and MAPK/ERK pathway dynamics, unveiling potential influences on tumor cell proliferation, survival, and drug sensitivity. This model enables dissection of HOMER2??s role in a cancer context, particularly concerning EGFR-targeted therapies.
These polyclonal knockout cells support a diverse range of research applications, including cancer biology, neuroscience, immunology, and drug target validation. Key assays include Western blotting and RT-qPCR for knockout confirmation, calcium flux and NFAT luciferase reporter assays for signaling studies, co-immunoprecipitation and immunofluorescence for protein interaction analysis, and flow cytometry for single-cell phenotyping. Additionally, drug sensitivity assays can evaluate therapeutic responses. For further information or procurement, please contact Ascent Research.
