The CCDC6 Knockout 786-O Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 786-O renal cell carcinoma line, with targeted disruption of the CCDC6 gene. This polyclonal pool provides a heterogeneous loss-of-function model for investigating CCDC6-dependent biology in a cancer-relevant epithelial background. It is designed for applications requiring a mixed knockout population without clonal selection, enabling broad functional studies.
The parental 786-O cell line was established from a primary clear cell renal cell carcinoma and harbors a well-characterized VHL tumor-suppressor gene mutation, rendering it defective in HIF?? regulation. These adherent epithelial cells are widely used to model clear cell RCC, a subtype representing the majority of kidney cancers, and they exhibit key signaling alterations relevant to tumor hypoxia responses and metabolic reprogramming. This background provides a relevant context for studying CCDC6??s role in renal carcinoma pathogenesis.
CCDC6 encodes a coiled-coil domain-containing protein that functions as a substrate of the ATM kinase in the DNA damage response. Upon genotoxic stress, ATM phosphorylates CCDC6, which modulates its interaction with PP4 phosphatase and promotes p53-dependent transcription of pro-apoptotic genes such as BAX, while repressing anti-apoptotic BCL2 family members. CCDC6 also interacts with CREB1, forming complexes that regulate apoptotic gene expression. Key downstream effectors include p53, CHK2, ??H2AX, and caspase activation cascades, positioning CCDC6 at a critical node linking DNA damage sensing to cell death.
In the context of 786-O cells, loss of CCDC6 impairs the DNA damage-induced apoptotic checkpoint, providing a model for how genomic instability may be tolerated in VHL-mutant renal carcinomas. Given that clear cell RCC often exhibits resistance to conventional therapies that rely on DNA damage and apoptosis, this polyclonal knockout population enables dissection of CCDC6??s role in chemotherapeutic sensitivity and DNA repair pathway interactions. The combination of VHL deficiency and CCDC6 disruption may synergistically influence tumor progression and drug response phenotypes.
Typical research applications include western blotting and RT-qPCR to validate CCDC6 disruption and assess expression of downstream targets (p53, BAX, BCL2), immunofluorescence analysis of ??H2AX foci to quantify DNA double-strand breaks, apoptosis assays using annexin V/PI staining, and cell viability or colony-formation assays after exposure to DNA-damaging agents or targeted therapies. This model also supports drug sensitivity screens to identify agents that bypass the apoptotic defect. For additional information or to request a technical consultation, please contact Ascent Research.
