The CCN2 Knockout DLD-1 Polyclonal Cells are a heterogeneous population of DLD-1 colorectal adenocarcinoma epithelial cells with CRISPR/Cas9-mediated disruption of the CCN2 gene. This polyclonal knockout population, arising from bulk transfection without clonal isolation, provides a loss-of-function model that avoids clonal selection artifacts and is representative of population-level gene function. The cells enable robust studies of the matricellular protein CCN2 (CTGF), which is implicated in cancer progression and fibrotic tissue remodeling.
DLD-1 is a human colorectal adenocarcinoma epithelial cell line harboring APC and KRAS mutations and p53 deficiency, reflecting common colorectal cancer alterations. APC mutations lead to constitutive Wnt/??-catenin pathway activation, KRAS mutations hyperactivate the MAPK/ERK cascade, and p53 loss ablates critical tumor suppressor responses, together recapitulating aggressive colorectal cancer phenotypes. These features make DLD-1 a widely used platform for investigating tumorigenesis, metastasis, and therapeutic resistance.
CCN2 is a secreted matricellular protein that modulates cell adhesion, migration, proliferation, and ECM production. Its expression is induced by upstream stimuli including TGF-??, mechanical stress, hypoxia, and Angiotensin II. CCN2 interacts with integrins (??v??3, ??5??1), LRP1, fibronectin, BMP-4, and receptor tyrosine kinases, and engages downstream effectors such as SMAD2/3, YAP/TAZ, ERK1/2, and AKT. It promotes expression of collagen, fibronectin, MMPs, and VEGF, thereby coordinating fibrotic, angiogenic, and migratory responses critical for tumor-stromal interactions.
In DLD-1 cells, CCN2 knockout impairs TGF-??-driven fibrotic signaling and may disrupt tumor-stromal crosstalk essential for colorectal cancer progression. With the APC/KRAS/p53 mutant background and expression of relevant integrins, loss of CCN2 allows specific dissection of its roles in EMT, collective migration, and ECM remodeling, distinct from canonical Wnt or MAPK hyperactivation. This polyclonal population provides a clinically pertinent system for studying CCN2-mediated mechanotransduction, including YAP/TAZ regulation, and the integration of mechanical and biochemical cues in colorectal adenocarcinoma.
Applications include colorectal cancer metastasis, tumor microenvironment analysis, fibrosis signaling, ECM remodeling, and drug resistance studies. Representative assays include Western blotting for CCN2 and SMAD phosphorylation, Transwell migration/invasion, collagen gel contraction, and RNA-seq for ECM gene expression profiling. The cells are also suitable for co-culture experiments to model tumor-stromal interactions, high-content imaging of ECM organization, and screening of anti-fibrotic or anti-metastatic compounds. TGF-?? stimulation assays can evaluate pathway responsiveness. For further information, please contact Ascent Research.
