GPSM1 knockout A-549 polyclonal cells are a CRISPR/Cas9-edited polyclonal cell population derived from the A-549 lung adenocarcinoma line, targeting the GPSM1 gene. This product comprises a heterogeneous pool of non-clonal cells harboring diverse loss-of-function mutations across the GPSM1 coding region, enabling robust analysis of GPSM1-dependent functions. As a polyclonal knockout model, it retains population-level heterogeneity, making it particularly suitable for cancer biology and signaling studies without the biases introduced by single-cell cloning.
The parental A-549 cell line is an adherent human alveolar basal epithelial model of non-small cell lung carcinoma (NSCLC) with wild-type KRAS and p53 alleles. Unlike many NSCLC lines that carry oncogenic KRAS or p53 mutations, A-549 provides a genetically unperturbed background for studying tumor-suppressive and oncogenic pathways. Its epithelial morphology and well-characterized signaling landscape make it a standard host for cancer cell biology, drug response, and signal transduction research.
GPSM1 functions as a guanine nucleotide dissociation inhibitor (GDI) that stabilizes the inactive GDP-bound state of G??i subunits (GNAI1/2/3), suppressing GPCR-dependent and -independent G-protein signaling. In mitotic spindle orientation, GPSM1 assembles a cortical complex with G??i-GDP, GPSM2/LGN, NUMA1, and Inscuteable (INSC), linking spindle poles to polarity cues. GPSM1 also promotes autophagy by inhibiting mTORC1, acting upstream of the ULK1 complex, and regulates cell migration and invasion through G?¦? effectors. Upstream, GPSM1 expression is activated by Wnt/??-catenin signaling and regulated by mTORC1 and ubiquitin-mediated degradation. Downstream, it modulates cAMP levels via adenylate cyclase, interacts with PI3K/AKT signaling, and influences planar cell polarity and Notch pathway crosstalk.
In A-549 lung adenocarcinoma cells, GPSM1 knockout enables dissection of its roles in asymmetric division, autophagy-dependent survival, and metastasis without confounding KRAS or p53 mutations. The wild-type p53 backdrop permits analysis of autophagy regulation under genotoxic stress, while the absence of constitutive RAS signaling allows clear investigation of GPSM1-driven migration and invasion. This model is ideal for exploring how spindle orientation defects contribute to aneuploidy and tumor heterogeneity, and for studying GPSM1’s integration with planar cell polarity and Notch pathways in epithelial cancers.
Key applications include high-content imaging of spindle/NuMA, transwell migration/invasion assays, and autophagy flux measurements by LC3 turnover. Biochemical validation employs co-immunoprecipitation of the GPSM1-G??i-GPSM2 complex, cAMP assays, and phospho-AKT immunoblotting. The polyclonal population is also suited for GPCR-independent signaling studies and small-molecule screens targeting spindle orientation defects. For technical or purchasing inquiries, please contact Ascent Research.
