The CCDC88C Knockout HAP1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population targeting the CCDC88C gene in the HAP1 human near-haploid cell line. This loss-of-function model enables pooled genetic studies and pathway analysis without clonal selection constraints, providing a robust system for dissecting CCDC88C function in Wnt signaling and related cellular processes.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) line. Its haploid genome simplifies genetic manipulation and yields unambiguous phenotypes in functional genomics screens, drug-gene interaction studies, and signal transduction analyses. The CML origin provides a leukemic context for investigating oncogenic pathways, while near-haploidy ensures consistent editing across the polyclonal population.
CCDC88C (Daple) negatively regulates canonical Wnt/??-catenin signaling by binding Dishevelled (DVL1, DVL2, DVL3), preventing ??-catenin stabilization and TCF/LEF-dependent transcription. Concurrently, it modulates non-canonical Wnt/planar cell polarity (PCP) pathways, influencing downstream effectors JNK, RhoA, Rac1, and c-Jun to govern directional cell migration and polarity. Upstream WNT ligands bind Frizzled receptors, and the destruction complex kinases CK1 and GSK3?? phosphorylate DVL, where CCDC88C competes with other partners, acting as an interface between canonical and non-canonical Wnt outputs.
In the HAP1 near-haploid background, CCDC88C knockout eliminates functional redundancy from a second allele, ensuring unambiguous loss-of-function phenotypes ideal for high-throughput screening. Derived from chronic myeloid leukemia, these cells recapitulate aspects of Wnt-driven oncogenic signaling, with documented links between CCDC88C alterations and colorectal, gastric, and hepatocellular carcinomas, as well as spinocerebellar ataxia. This model thus supports translational studies in Wnt-dependent cancer progression and neurodegenerative mechanisms.
Typical experimental protocols include TOP/FOP Wnt reporter assays to measure ??-catenin/TCF activity, western blotting for ??-catenin stabilization, Sanger sequencing and RT?qPCR for knockout validation, cell migration and invasion assays to assess PCP function, co?immunoprecipitation with DVL1, CK1, or GSK3??, and immunofluorescence for subcellular localization. The polyclonal population is suited for functional genomics screens and drug target discovery against Wnt pathway components. For more details, please contact Ascent Research.
