The ITGB3 Knockout 769-P Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population targeting the human ITGB3 gene in the 769-P renal cell carcinoma background. This heterogenous pool of gene-disrupted cells serves as a robust loss-of-function model, circumventing clonal artifacts while enabling systematic interrogation of integrin beta-3-dependent phenotypes. The polyclonal format offers a powerful tool for high-content studies where population-level responses are critical.
The 769-P cell line is a widely used model of human clear cell renal cell carcinoma, isolated from a primary epithelial tumor. These adherent cells retain hallmark features of renal cancer, including dysregulated metabolic and signaling pathways, and are extensively employed to investigate tumorigenesis, invasion, and drug responses. Their genetic tractability makes them an ideal host for CRISPR-mediated gene editing.
ITGB3 encodes the integrin beta-3 subunit, which pairs with alpha V (ITGAV) or alpha IIb (ITGA2B) to form heterodimeric receptors for vitronectin, fibrinogen, and fibronectin. Ligand binding initiates intracellular signaling through focal adhesion kinase (FAK) and Src, activating downstream PI3K-Akt and MAPK-ERK cascades, as well as Rho GTPases such as RhoA and Rac1. Integrin beta-3 activity is regulated by upstream cues including TGF-??, VEGF, thrombin, and SDF-1/CXCL12, and its expression is driven by the transcription factor RUNX1. The beta-3 subunit also interacts with adaptor proteins talin and kindlin, and associates with CD47 and growth factor receptors (PDGFR, VEGFR), positioning it as a hub for adhesion and growth factor signaling.
In the 769-P renal carcinoma background, CRISPR-mediated disruption of ITGB3 eliminates integrin beta-3?Cmediated adhesion and attenuates critical oncogenic signaling pathways. Loss of beta-3 impairs cell attachment to vitronectin and other ECM ligands, reducing FAK and Src phosphorylation, and dampening PI3K-Akt and ERK1/2 activation. This model thus enables dissection of how renal carcinoma cells exploit integrin signaling for migration, survival, and metastatic colonization, and it provides a platform to assess the dependency of tumor cells on beta-3-mediated interactions.
Key applications of these polyclonal knockout cells encompass studies of integrin-mediated adhesion and signaling in renal carcinoma, tumor metastasis mechanisms, drug target validation for anti-angiogenic or anti-metastatic agents, and functional complementation assays. Representative experiments include western blotting for ITGB3, flow cytometry for surface integrins, cell adhesion and migration assays (Boyden chamber), phospho-FAK/Src analysis, and co-immunoprecipitation. For further information, please contact Ascent Research.
