The KCTD9 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with targeted disruption of the KCTD9 gene, providing a loss-of-function model derived from the human 769-P renal cell carcinoma line. These polyclonal knockout cells harbor heterogeneous gene-editing events, enabling robust, population-level analysis of KCTD9-dependent processes without clonal artifacts.
Derived from a clear cell renal cell carcinoma (ccRCC), the 769-P parental line is an epithelial model extensively used in renal cancer research to study tumor biology, drug responses, and oncogenic signaling. Its genetic background mimics key aspects of ccRCC, making it a relevant host for examining KCTD9 function in a disease-relevant context.
KCTD9 acts as a substrate-specific adaptor for the Cullin3-RING E3 ubiquitin ligase (CRL3), recruiting proteins such as TRIF (TICAM1) and ??-catenin (CTNNB1) for ubiquitination and proteasomal degradation. By targeting TRIF, KCTD9 negatively regulates Toll-like receptor (TLR)-mediated NF-??B signaling, while ??-catenin degradation suppresses Wnt pathway activity. KCTD9 activity is modulated by CUL3 neddylation and inflammatory cytokines (TNF-??, IL-1??). In knockout cells, accumulation of TRIF and ??-catenin leads to constitutive NF-??B and Wnt activation, offering a defined system to study these cascades.
Loss of KCTD9 has been linked to ccRCC progression through sustained Wnt-driven proliferation and inflammatory signaling. The 769-P KCTD9 knockout model enables dissection of its tumor-suppressive roles, including effects on apoptosis, cell cycle regulation, and epithelial-mesenchymal transition, and facilitates identification of potential therapeutic targets within the ubiquitin-proteasome or downstream signaling networks.
These polyclonal knockout cells are compatible with assays such as Western blotting, co-immunoprecipitation, ubiquitination assays, and RT-qPCR to monitor CRL3 complex activity and target expression. Functional readouts include TOP/FOP Flash and NF-??B luciferase reporters, cell proliferation (MTT, BrdU), apoptosis (Annexin V), and migration/invasion studies. They are ideal for synthetic lethality screens, biomarker discovery, and compound profiling in ccRCC. For further information, please contact Ascent Research.
