The GPR180 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for the disruption of the GPR180 gene in the human NCI-H1975 lung adenocarcinoma cell line. This product provides a heterogeneous pool of cells harboring targeted gene disruptions introduced by CRISPR/Cas9, generating a loss-of-function model for studying GPR180 biology.
The NCI-H1975 cell line is derived from a female non-smoker with lung adenocarcinoma and is widely used as a model for non-small cell lung cancer (NSCLC). This adherent epithelial line serves as a relevant platform for investigating oncogenic signaling pathways and evaluating therapeutic interventions in a lung cancer context.
GPR180 is an orphan G protein-coupled receptor predicted to couple to heterotrimeric G proteins (G??s/i/q) and modulate downstream effectors such as adenylyl cyclase, phospholipase C, and the MAPK/ERK and PI3K/Akt signaling cascades. Downstream targets include MAPK, Akt, and transcriptional regulators that drive cell proliferation and survival. GPR180 is thought to interact with ??-arrestin and G proteins to propagate signals from extracellular stimuli, although its ligand remains unknown. Knockout of GPR180 is expected to attenuate these signaling pathways, reducing downstream phosphorylation of ERK and Akt and thereby impairing oncogenic signaling in tumor cells.
In the context of lung adenocarcinoma, GPR180 signaling is implicated in promoting tumor cell growth and survival. Disruption of GPR180 function in NCI-H1975 cells provides a model to dissect the contribution of orphan GPCR signaling to cancer phenotypes. By eliminating GPR180 expression, researchers can interrogate the dependency of NSCLC cells on this receptor-driven pathway and assess changes in downstream signal transduction, cell cycle progression, and apoptotic responses. This polyclonal population retains the genetic heterogeneity typical of polyclonal knockout pools, enabling robust phenotypic screening without the biases of single-clone selection.
Researchers can employ these GPR180 knockout cells in a variety of applications, including functional characterization of orphan GPCRs, investigation of lung cancer signal transduction mechanisms, and drug target discovery. Representative assays include western blotting for phospho-ERK and phospho-Akt to assess pathway activity, MTT or BrdU proliferation assays, transwell migration assays, flow cytometric analysis of apoptosis via Annexin V staining, and RNA-seq transcriptional profiling to identify global expression changes. Additionally, these cells are suitable for drug sensitivity screens, including treatments with EGFR inhibitors, to evaluate the role of GPR180 in therapeutic response. For further details, please contact Ascent Research.
