The GPER1 Knockout DLD-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from DLD-1 human colorectal adenocarcinoma cells, offering targeted disruption of the GPER1 gene for loss-of-function studies. The polyclonal format provides a genetically diverse pool of edited cells, minimizing clonal selection bias and enabling robust phenotypic analysis.
DLD-1 is a well-characterized colorectal adenocarcinoma line harboring inactivating mutations in APC and TP53, along with an activating KRAS mutation. These genetic lesions drive constitutive Wnt/??-catenin signaling, genomic instability, and MAPK pathway activation, rendering the cells highly tumorigenic. As an epithelial model, DLD-1 recapitulates key hallmarks of colorectal cancer progression and is widely used for mechanistic and translational research.
GPER1 is a seven-transmembrane GPCR that mediates rapid, non-genomic estrogen signaling. Upon binding 17??-estradiol or the agonist G-1, it activates G??s and G??i, leading to EGFR transactivation and phosphorylation of ERK1/2 and AKT. Src kinases facilitate this crosstalk, while G??s stimulates cAMP/PKA. ??-arrestin and caveolin-1 act as scaffolds. Downstream targets include c-Fos, cyclin D1, and MMPs, driving proliferation, migration, and survival. GPER1 expression is also modulated by hypoxia and EGF.
In colorectal cancer, GPER1 promotes tumor progression through estrogen-driven non-genomic signals. The DLD-1 background, with mutant APC, KRAS, and TP53, provides a clinically relevant context to study how GPER1 crosstalk with EGFR amplifies MAPK and AKT activity, potentially enhancing KRAS-driven oncogenesis, while cAMP/PKA modulation may intersect with ??-catenin signaling. Since DLD-1 cells lack ER??, this knockout model enables specific dissection of GPER1-dependent effects on proliferation, survival, and motility, making it valuable for investigating ER??-independent estrogen actions and endocrine resistance mechanisms.
Typical applications include estrogen-stimulated signaling assays (phospho-ERK/AKT western blotting), gene expression analysis by RT-qPCR, and cell-based readouts such as MTT proliferation, wound-healing migration, and transwell invasion assays. The cells are also suitable for immunofluorescence, colony formation, and xenograft tumor growth studies. They can be used in drug screening to validate GPER1 modulators like tamoxifen or G-1. For further information, please contact Ascent Research.
