The CD44 Knockout 769-P Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human renal cell carcinoma line 769-P. This loss-of-function model enables systematic investigation of CD44-dependent cellular processes. By disrupting the CD44 gene across a heterogeneous cell pool, researchers can study population-level consequences of CD44 ablation without clonal isolation artifacts. The polyclonal format recapitulates the genetic heterogeneity inherent in tumor biology, making it particularly suitable for mechanistic studies of signaling networks and phenotypic screening.
The parental 769-P cell line was established from a primary clear cell renal cell carcinoma, a common kidney cancer subtype associated with biallelic inactivation of the VHL tumor suppressor gene. Loss of functional pVHL leads to stabilization of hypoxia-inducible factors (HIFs), driving a pseudohypoxic transcriptional program that promotes angiogenesis, metabolic reprogramming, and invasive growth. As a well-characterized model of renal cancer, 769-P cells retain key oncogenic features, including robust proliferation and migration capacity, providing a disease-relevant background for studying genes implicated in tumor progression such as CD44.
CD44 encodes a transmembrane glycoprotein that serves as the principal cell surface receptor for hyaluronic acid (HA), a major extracellular matrix component. HA binding induces conformational changes in CD44 that facilitate recruitment of intracellular adaptor proteins and SRC family kinases, triggering signaling cascades such as RAS?CPI3K?CAKT, MAPK/ERK??mediated by ERK1/2 and AKT??, NF-??B, and Wnt/???catenin. Upstream regulators hyaluronic acid, TNF???, EGF, HGF, and IL?1?? potentiate these pathways. Downstream, CD44 signaling elevates expression of matrix metalloproteinases MMP?2 and MMP?9, cyclin D1, and c?Myc, while recruiting ezrin/radixin/moesin (ERM) proteins to drive cytoskeletal reorganization. Together, these events promote cell proliferation, survival, adhesion, migration, and invasion.
In the context of the VHL-mutant 769-P cell line, CD44 is poised to intersect with hypoxia-driven pathways that sustain renal carcinoma aggressiveness. The loss of VHL function elevates HIF?1?? and HIF?2?? levels, which can upregulate CD44 expression, creating a positive feedback loop that amplifies HA-dependent signaling. Consequently, CD44 likely contributes to epithelial?mesenchymal transition (EMT), metastatic dissemination, and chemoresistance in clear cell renal cell carcinoma. The CD44 Knockout 769-P Polyclonal Cells thus provide an ideal platform to dissect tumor-intrinsic functions of this receptor, examine its crosstalk with the VHL?CHIF axis, and evaluate its role in hyaluronan?mediated extracellular matrix remodeling.
This knockout model is suitable for cancer metastasis assays, including Boyden chamber migration and Matrigel invasion, as well as cell adhesion and hyaluronic acid binding studies. Flow cytometry, western blotting, immunofluorescence, RNA?seq, and RT?qPCR enable phenotypic and transcriptomic analysis. Applications encompass hyaluronan signaling, drug resistance, EMT, and renal cancer biology. For further information, please contact Ascent Research.
