The ADAM10 Knockout 786-O Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population derived from the human 786-O renal clear cell carcinoma cell line. This product comprises a genetically diverse pool of cells carrying targeted disruptions in the ADAM10 gene, introduced by transient delivery of Cas9 and ADAM10-specific guide RNA. The polyclonal format minimizes clonal selection artifacts and provides a biologically relevant loss-of-function model for studying ADAM10-dependent processes. These cells are supplied as a characterized population for direct use in functional assays.
The parental 786-O cell line was established from a primary clear cell renal adenocarcinoma of a 58-year-old male patient. It is widely utilized in kidney cancer research due to its characteristic VHL gene inactivation and consequent stabilization of hypoxia-inducible factors, which drive angiogenesis and metabolic reprogramming. The cell line??s mesenchymal-like features and invasive properties make it an effective platform for probing epithelial-mesenchymal transition and metastatic dissemination. Introduction of ADAM10 knockout into this defined genetic context enables precise interrogation of the protease??s role in renal carcinoma pathobiology.
ADAM10 is a transmembrane metalloproteinase that sheds Notch receptors, APP, E-cadherin, CD44, and IL-6R. It is activated by TGF-??, TNF-??, PKC, calcium influx, and ERK signaling. Notch cleavage releases NICD, which partners with RBP-J?? to drive HES1 and HEY1 transcription. APP processing generates neuroprotective sAPP??, whereas ??-amyloid formation requires subsequent ??-secretase activity. E-cadherin shedding disrupts adhesion and yields a fragment that enhances migration through ??-catenin. CD44 and IL-6R processing promote tumor growth and trans-signaling, respectively. Tetraspanins Tspan12, Tspan15, and Tspan33, along with ADAM17, modulate ADAM10 activity.
In the 786-O carcinoma background, ADAM10 disruption abolishes Notch signaling by preventing NICD generation, leading to loss of HES1 and HEY1 expression. Reduced E-cadherin shedding strengthens adherens junctions and may impede ??-catenin-mediated invasion. Diminished processing of CD44 and IL-6R is anticipated to blunt pro-tumorigenic cues and cytokine trans-signaling. Consequently, this model enables systematic examination of ADAM10-dependent proteolytic networks that sustain renal carcinoma progression and highlights its potential as a therapeutic vulnerability.
This knockout product supports diverse research applications, including functional analysis of Notch pathway alterations in kidney cancer, validation of ADAM10 as a target for Alzheimer??s and inflammatory diseases, and mechanistic studies of cell adhesion and migration. Standard assays include Western blotting for ADAM10, NICD, and E-cadherin fragments; RT-qPCR for HES1 and HEY1; scratch-wound and transwell migration assays; E-cadherin-based adhesion tests; ELISA for sAPP??; flow cytometry for surface protein profiling; and RNA-seq for global transcriptomic changes. For detailed protocols or assistance, please contact Ascent Research.
