The DYRK1A Knockout HCT 116 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population in which the DYRK1A gene has been disrupted. This pool of edited cells provides a loss-of-function model free of clonal selection biases, enabling robust investigation of DYRK1A-dependent processes in a genetically diverse colorectal carcinoma background.
The HCT 116 parental line is a near-diploid, microsatellite-stable colorectal carcinoma model harboring KRAS G13D and PIK3CA H1047R mutations. These epithelial cells retain robust tumorigenic properties and are widely used to investigate signaling pathways relevant to colorectal cancer biology, including MAPK/ERK and PI3K/AKT cascades.
DYRK1A encodes a dual-specificity kinase that phosphorylates substrates such as NFATc transcription factors, tau, FOXO, STAT3, and p53. Its activity is modulated by growth factor signaling, calcium, and transcriptional control by E2F1. DYRK1A functions as a central integrator of the MAPK/ERK, NFAT, WNT/??-catenin, and Notch pathways, interacting with DCAF7/WDR68 and HIPK2 to regulate gene expression programs controlling proliferation, differentiation, and survival. Disruption of DYRK1A in HCT 116 cells abolishes phosphorylation-dependent regulation of NFATc nuclear transport, potentially altering transcription of target genes involved in cell cycle progression and apoptosis, and may blunt STAT3-driven oncogenic signaling.
In the context of colorectal carcinoma, DYRK1A knockout can impair tumorigenic phenotypes by disrupting proliferation and survival signals mediated through NFAT and STAT3 pathways. The constitutively active KRAS and PIK3CA mutations in HCT 116 cells provide a sensitized background to study DYRK1A-dependent resistance mechanisms and to identify synthetic lethal interactions. Additionally, because DYRK1A is implicated in Down syndrome and Alzheimer’s disease, this model enables cross-disciplinary investigations linking neurodevelopmental kinase function to cancer cell biology. This model is thus valuable for evaluating DYRK1A-targeted therapies and for uncovering context-specific functions of DYRK1A in oncogene-driven malignancies.
These polyclonal knockout cells are compatible with a range of analytical techniques, including western blotting, RT-qPCR, and immunofluorescence for assessing DYRK1A loss and downstream target modulation, as well as phospho-signaling analysis, proliferation, migration, invasion, and flow cytometry-based cell-cycle profiling. The model is suitable for drug target validation, synthetic lethality screens, and mechanistic studies. For technical specifications or ordering information, please contact Ascent Research.
