The GPSM2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population produced by disrupting the GPSM2 locus in the NCI-H1975 human lung adenocarcinoma line. This heterogeneous knockout pool provides a loss-of-function system for studying GPSM2-dependent mitotic spindle orientation, cell polarity, and signaling without single-cell cloning, making it suitable for population-level functional genomics screens and mechanistic assays.
NCI-H1975 is a non-small cell lung cancer (NSCLC) model derived from the adenocarcinoma of a non-smoking female. The cells carry endogenous EGFR L858R and T790M mutations, which drive persistent kinase activity and confer resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). This genetic background makes NCI-H1975 a key tool for investigating EGFR-driven oncogenesis and acquired drug resistance.
GPSM2 (LGN) is a scaffold protein that bridges heterotrimeric G protein signaling to the cortical force-generating apparatus. It directly binds G??i-GDP (GNAI1/2/3) and NuMA, recruiting dynein/dynactin to the cell cortex to generate pulling forces that orient the mitotic spindle. Upstream, GPSM2 engagement is regulated by G protein-coupled receptors, CDK1 phosphorylation, and polarity determinants such as Inscuteable and DLG1. Disruption of GPSM2 alters spindle positioning, which can affect Hippo pathway activity??MST1/2 and LATS1 kinases phosphorylate and inactivate YAP/TAZ transcriptional coactivators??thereby linking division orientation to cell fate and proliferation.
In NCI-H1975 cells, GPSM2 knockout is expected to perturb mitotic spindle orientation, potentially affecting asymmetric division and epithelial polarity within the context of EGFR-mutant NSCLC. Because Hippo pathway effectors YAP/TAZ are implicated in TKI resistance and tumor progression, loss of GPSM2 may reveal crosstalk between spindle machinery and drug sensitivity mechanisms. This model enables investigation of how polarity and division control intersect with oncogenic EGFR signaling.
Researchers can employ the GPSM2 Knockout NCI-H1975 Polyclonal Cells for live-cell imaging of mitotic dynamics, immunofluorescence-based analysis of NuMA/dynein cortical localization, EGFR TKI dose?Cresponse assays, colony formation, and western blotting or qPCR assessment of Hippo pathway targets. The polyclonal knockout pool also facilitates drug-screening campaigns aimed at identifying modulators of spindle orientation or YAP/TAZ activity. For further information, please contact Ascent Research.
