The ADAMTS14 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which ADAMTS14 has been disrupted in the 786-O human renal cell carcinoma line, providing a loss-of-function model for investigating extracellular matrix remodeling and collagen processing. This polyclonal format avoids clonal selection artifacts and captures the natural heterogeneity of editing outcomes, making it suitable for robust functional studies.
The 786-O host cell line is a well-characterized epithelial model of clear cell renal cell carcinoma (ccRCC) with a mutant VHL gene, leading to dysregulated hypoxia pathways and a tumorigenic phenotype. These cells are routinely used in kidney cancer research to examine tumor-microenvironment interactions, metastatic behavior, and drug sensitivity.
ADAMTS14 encodes a secreted metalloproteinase critical for procollagen I and II processing, a requisite step in collagen fibril assembly and ECM organization. Upstream, TGFB1 activates ADAMTS14 through SMAD2/3 transcription factors, and mechanical stretch further induces its expression. The enzyme interacts directly with its propeptide substrates and is inhibited by TIMP3. Following cleavage, mature collagen fibers polymerize, elevating matrix rigidity and engaging integrins, which transduce signals via focal adhesion kinase (FAK) to influence cell adhesion, migration, and proliferation.
In 786-O cells, loss of ADAMTS14 is expected to disrupt procollagen processing, resulting in diminished mature collagen deposition and reduced matrix stiffness. This likely attenuates integrin-mediated FAK signaling, potentially impairing cell adhesion, migration, and invasion??key traits of metastatic progression. Given the VHL-mutant background that already perturbs hypoxia-responsive pathways, ADAMTS14 knockout offers a refined system to dissect the interplay between ECM biophysics and oncogenic signaling in renal cell carcinoma.
The ADAMTS14 knockout polyclonal cells are amenable to a range of applications, including collagen gel contraction assays to assess ECM remodeling force, migration and invasion assays to evaluate metastatic potential, and cell adhesion assays to probe integrin function. ECM staining and mass spectrometry can quantify collagen processing defects, while Western blotting and RT-qPCR confirm ADAMTS14 disruption and downstream target expression. These cells are particularly useful for fibrosis drug testing, TGF-?? pathway studies, and ECM stiffness research. For further information, please contact Ascent Research.
