The DCC Knockout SW480 Cell Line is a CRISPR/Cas9-edited human colorectal adenocarcinoma cell product in which the DCC gene has been disrupted to create a loss-of-function model. This knockout cell line enables investigation of DCC-dependent signaling mechanisms in a well-characterized intestinal epithelial background.
The parental SW480 cell line was originally established from a Dukes’ type B colorectal adenocarcinoma and is widely employed in colorectal cancer research. SW480 cells carry oncogenic mutations in APC, KRAS, and TP53, rendering them a robust platform for studying genetic interactions and tumor suppressor pathways in a disease-relevant context.
DCC encodes a transmembrane dependence receptor for the guidance cue netrin-1 (NTN1). In the presence of NTN1, DCC activates downstream survival and migratory signaling through PI3K/AKT and MAPK/ERK pathways, engaging effectors such as AKT, ERK1/2, FAK, and Rho GTPases including RhoA and Rac1. Unliganded DCC, however, triggers apoptosis by recruiting and activating caspase-9, which subsequently processes caspase-3. DCC also heterodimerizes with UNC5 family receptors (UNC5A?CD) to modulate divergent signaling outcomes, and interacts with adaptor proteins such as DIP13??/APPL1. Epigenetic silencing of DCC, frequently mediated by promoter methylation and DNA methyltransferases, constitutes a known mechanism of tumor suppressor inactivation in colorectal cancers.
In the SW480 background, which already harbors defects in APC, KRAS, and TP53, disruption of DCC eliminates its pro-apoptotic dependence receptor function, mimicking the epigenetic silencing observed in advanced colorectal tumors. This knockout thus provides a physiologically relevant system to dissect how loss of netrin-1/DCC-mediated apoptotic signaling cooperates with other oncogenic alterations to promote tumor progression, chemoresistance, and metastatic behavior.
Researchers can employ this cell line in a variety of functional assays, including Western blotting and RT-qPCR to confirm DCC ablation and monitor caspase-3, caspase-9, or AKT/ERK phosphorylation status; Annexin V/propidium iodide apoptosis assays; Transwell migration and invasion studies; co-immunoprecipitation of DCC with NTN1 or UNC5 receptors; immunofluorescence; and xenograft tumor growth models. Additional applications include drug screening for netrin-1 pathway modulators and epigenetic reactivation studies using DNA methylation inhibitors. For additional details or custom project inquiries, please contact Ascent Research.
