The KDR Knockout A-549 Polyclonal Cells are a human lung carcinoma cell population generated by CRISPR/Cas9-mediated disruption of the KDR gene, which encodes vascular endothelial growth factor receptor 2 (VEGFR2). This polyclonal product contains a mix of cells harboring diverse loss-of-function edits at the KDR locus, providing a ready-to-use model for studying VEGFR2-dependent signaling pathways in a cancer-relevant background without the need for single-cell cloning.
The host A-549 cell line was originally derived from the alveolar basal epithelium of a 58-year-old male with pulmonary adenocarcinoma. As an adherent epithelial line, A-549 cells recapitulate key features of non-small cell lung cancer, including activation of oncogenic pathways such as MAPK/ERK and PI3K-AKT. Their robust growth, defined karyotype, and extensive use in cancer biology make them a standard model for lung adenocarcinoma research, drug discovery, and functional genomics studies.
KDR (VEGFR2) is a transmembrane tyrosine kinase and the primary receptor for VEGFA, also binding VEGFC and VEGFD. Ligand binding induces dimerization and autophosphorylation, recruiting adaptors like Shb and activating downstream pathways including PI3K-AKT and MAPK/ERK. Key phosphorylated targets include AKT, ERK, Src, FAK, and p38MAPK, which regulate proliferation, survival, and migration. VEGFR2 interacts with coreceptors NRP1 and integrins, and forms complexes with VE-cadherin. Its expression is upregulated by hypoxia-inducible factors.
KDR knockout in A-549 cells abolishes VEGF-dependent activation of AKT and ERK, impairing pro-survival and pro-migratory signaling. This reduces proliferation, invasion, and anchorage-independent growth. Loss of VEGFR2 also disrupts integrin-mediated focal adhesion dynamics, altering cell motility. Thus, this model enables investigation of VEGFR2’s role in lung tumor epithelial cells, including contributions to metastasis and therapy resistance.
Applications include anti-angiogenic drug screening, mechanistic studies of VEGF-independent tumor growth, and tumor microenvironment research. Standard assays comprise Western blotting for phospho-proteins, RT-qPCR, migration/invasion transwell tests, VEGF-stimulated viability assays, and xenograft models. For technical assistance, contact Ascent Research.
