CASZ1 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the 786-O renal cell carcinoma line, with stable disruption of the CASZ1 gene. This loss-of-function model provides a defined background to study the tumor-suppressive roles of CASZ1 in clear cell renal cell carcinoma (ccRCC). The heterogeneous editing outcomes of the polyclonal pool enable population-level phenotypic analysis without clonal bias, appropriate for interrogating CASZ1-dependent molecular changes in the VHL-mutant context.
The 786-O cell line is a standard ccRCC model harboring a homozygous VHL mutation that constitutively activates hypoxia-inducible factors (HIFs) and downstream angiogenic and metabolic programs. These cells exhibit epithelial morphology and dysregulation of TGF-??, Wnt, and Hippo pathways. The VHL-deficient, pro-oncogenic setting synergizes with CASZ1 loss, enhancing tumorigenic behaviors and offering a relevant system to examine interactions between tumor suppressor pathways and hypoxia-driven transcription.
CASZ1 is a zinc finger transcription factor and tumor suppressor that regulates cell cycle arrest, apoptosis, and epithelial-mesenchymal transition (EMT). It is controlled by upstream signals including E2F1 and TGF-??, and directly modulates targets like CDKN1A (p21), MYC, CDH1, and CDH2. CASZ1 forms complexes with DNMT3A, HDAC1, and NuRD components to repress transcription. Within signaling networks, CASZ1 interfaces with TGF-??/SMAD, Wnt/??-catenin (CTNNB1/TCF), Hippo (YAP/TAZ), and p53 pathways. Knockout likely de-represses MYC, reduces CDKN1A, and facilitates EMT via cadherin switching and MMP upregulation.
In 786-O cells, CASZ1 knockout collaborates with VHL loss to amplify oncogenic phenotypes. Constitutive HIF activity converges with CASZ1 deficiency to drive proliferation, survival, and invasion through enhanced TGF-?? and hypoxia-responsive programs. This model uncovers how CASZ1 normally restrains SMAD2/3, CTNNB1/TCF, and YAP/TAZ effectors and maintains epithelial integrity. The polyclonal composition mirrors tumor heterogeneity, supporting drug response assays and functional genomics screens.
These cells are suited for transcriptomic profiling (RNA-seq, RT-qPCR), protein analysis (Western blotting), ChIP-qPCR of target loci, and functional assays (proliferation, migration, apoptosis). Applications include dissecting CASZ1 tumor suppression, TGF-??/SMAD and Wnt/??-catenin signaling, and EMT regulation, as well as drug target validation and high-throughput screening for synthetic lethal interactions. For additional information, please contact Ascent Research.
