The HOMER1 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung adenocarcinoma NCI-H1975 cell line. This heterogeneous pool provides a loss-of-function model for HOMER1, a scaffold protein encoded by the HOMER1 gene. The polyclonal format enables robust phenotypic screening without clonal isolation, suitable for bulk functional genomic analyses.
The host NCI-H1975 line is an adherent epithelial line from a female non-smoker with lung adenocarcinoma. It harbors activating EGFR L858R and T790M mutations, rendering it a key model for EGFR-mutant non-small cell lung cancer (NSCLC). These cells exhibit tumorigenic properties in vitro and in vivo and are widely used in studies of oncogenic signaling, drug resistance, and metastasis.
HOMER1 functions as an adaptor that scaffolds group I metabotropic glutamate receptors (mGluR1/5) to downstream effectors, including IP3 receptors (IP3R) and Shank family proteins. This interaction couples glutamatergic stimulation to intracellular calcium release via the mGluR1/5?CHOMER1?CIP3R axis and links to MAPK/ERK and PI3K/AKT pathways through PI3K and other partners. HOMER1 is regulated by BDNF, glutamate, neuregulin, and EGFR signaling, and it interacts with TRPC1, drebrin, and Shank1/2/3. Downstream targets include ERK1/2, CREB, and mTOR, while it also participates in actin cytoskeletal remodeling through Shank.
In EGFR-mutant NCI-H1975 cells, HOMER1 may integrate glutamatergic signals with oncogenic pathways. By scaffolding mGluRs to ERK and AKT cascades, HOMER1 potentially influences proliferation and migration. Disruption of HOMER1 in this polyclonal model allows examination of cross-talk between glutamate receptors and EGFR-driven signaling, particularly effects on calcium dynamics, ERK1/2 phosphorylation, and PI3K/AKT/mTOR activity. This addresses the emerging role of synaptic scaffold proteins in cancer biology.
This HOMER1 knockout model supports diverse research applications, including functional genomics in NSCLC, drug target validation, and investigation of glutamatergic signaling in cancer. Typical assays include Western blotting and RT-qPCR for knockout confirmation, immunofluorescence for localization, proliferation (MTS/CCK-8) and Transwell assays for phenotype assessment, phospho-ERK/AKT analysis, RNA-seq, and EGFR inhibitor sensitivity testing. For more details, please contact Ascent Research.
