The ADAMTS14 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the NCI-H1703 human non-small cell lung carcinoma line, in which the ADAMTS14 gene has been disrupted. ADAMTS14 encodes a secreted metalloprotease that specifically cleaves the N-propeptides of procollagens I, II, and III, a crucial step in collagen fibrillogenesis and extracellular matrix (ECM) organization. This loss-of-function model provides a valuable tool to study the role of ADAMTS14 in lung adenocarcinoma biology.
The host cell line NCI-H1703 was established from a lung adenocarcinoma of a 54-year-old male smoker. It exhibits an epithelial phenotype, harbors wild-type KRAS and mutant p53, and is widely employed as a model for lung adenocarcinoma, particularly for drug sensitivity and resistance investigations. This well-characterized background offers a robust platform for exploring how ECM-modifying enzymes like ADAMTS14 influence tumor cell behavior.
ADAMTS14 activity is stimulated by TGF-??/SMAD signaling, pro-inflammatory cytokines such as IL-1?? and TNF-??, and mechanical cues, while its transcription is driven by Sp1. The protease interacts with procollagens, fibronectin, integrin ??2??1, and BMP1, and its activity is modulated by TIMP-1. Disruption of ADAMTS14 prevents N-propeptide cleavage, leading to defective collagen fibril assembly and altered integrin-mediated signaling, including FAK pathway activation, which impacts cell adhesion and migration.
In the context of NCI-H1703 cells, ADAMTS14 knockout allows researchers to dissect the contribution of collagen processing to lung adenocarcinoma progression. The polyclonal nature of the knockout population mitigates clonal selection artifacts and better reflects the heterogeneity of tumor cell responses. This model is particularly relevant for studying how ECM remodeling affects migration, invasion, and signaling in a KRAS wild-type, p53-mutant lung adenocarcinoma environment.
This product supports diverse applications including functional genomics, ECM biology, collagen processing studies, and drug screening. Typical assays for validation include western blotting for collagen fragments, RT-qPCR for ADAMTS14 and collagen genes, immunofluorescence for ECM proteins, collagen gel contraction, and migration/invasion assays. Transcriptome profiling via RNA-seq and protein interaction studies by co-immunoprecipitation can further characterize the knockout??s effects. For further information and technical support, please contact Ascent Research.
