The KRT14 knockout 769-P polyclonal cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the KRT14 gene in the human 769-P renal cell carcinoma line. This loss-of-function model enables the study of type I keratin KRT14 in epithelial cell biology. The polyclonal format provides a heterogeneous pool of gene-edited cells, facilitating robust functional studies without clonal selection artifacts. The product is suitable for investigating cytoskeletal dynamics and adhesion mechanisms in clear cell renal carcinoma contexts.
The 769-P host cell line is a widely used epithelial cell model derived from a human clear cell renal cell carcinoma. These cells are VHL-negative, recapitulating a hallmark of sporadic clear cell RCC, and exhibit characteristic epithelial morphology. The line??s genomic background supports the study of tumor suppressor pathways, hypoxia signaling, and metastatic behavior, making it a relevant platform for examining the role of keratins in renal cancer progression.
KRT14 encodes a type I keratin that pairs with its type II partner KRT5 to form intermediate filaments, critical for maintaining mechanical integrity in epithelial tissues. KRT14 is transcriptionally regulated by factors including TP63 and SOX2 and is responsive to extracellular cues mediated by EGFR, TGFB1, and WNT3A signaling. The KRT14 protein interacts with desmoplakin, plectin, and plakoglobin, anchoring intermediate filaments to desmosomes and hemidesmosomes. Downstream, KRT14 influences the localization and stability of integrin beta4 and modulates MMP9 expression, linking keratin networks to cell adhesion and matrix remodeling. Disruption of KRT14 thus dismantles the KRT5-KRT14 filamentous scaffold, impairing desmosomal and hemidesmosomal integrity and perturbing epithelial-mesenchymal transition (EMT) dynamics.
In the 769-P renal cell carcinoma model, KRT14 knockout has significant implications for tumor cell mechanics. The VHL-negative background of these cells is associated with constitutive HIF activation and altered adhesion protein expression, conditions under which keratin network disruption may further compromise cell?Ccell and cell?Cmatrix contacts. Loss of KRT14 is predicted to reduce mechanical stability, enhance migratory capacity, and potentially influence invasion through EMT-related pathways. This model can therefore help delineate how cytoskeletal defects intersect with oncogenic signaling in clear cell RCC, offering insights into mechanisms driving metastasis and therapeutic resistance.
Researchers can employ this knockout cell population for diverse experimental purposes, including immunofluorescence imaging of keratin network collapse, western blotting for EMT marker changes, scratch wound and Transwell invasion assays to quantify migration, and RT-qPCR profiling of mesenchymal gene expression. Co-immunoprecipitation experiments can assess altered interactions with desmoplakin or integrin beta4, while cisplatin sensitivity assays may reveal chemoresistance mechanisms linked to KRT14 status. This product is also applicable to modeling epidermolysis bullosa simplex-like adhesion defects and investigating breast cancer cell behavior. For further technical details, please contact Ascent Research.
