The DCC Knockout LoVo Cell Line is a CRISPR/Cas9-edited derivative of the human LoVo colon adenocarcinoma cell line, engineered with a targeted disruption of the DCC gene. This ablation creates a clean loss-of-function model for investigating the role of DCC as a tumor suppressor and netrin-1 dependence receptor in colorectal cancer biology, without the confounding effects of residual protein expression.
The parental LoVo cell line was originally established from a lymph node metastasis of a 56-year-old Caucasian male with colon adenocarcinoma, classified as Dukes’ type C. LoVo cells exhibit an adherent epithelial morphology and are widely recognized as a model for metastatic colorectal adenocarcinoma, enabling studies of tumor cell invasion, migration, and response to therapeutic agents in a clinically relevant genetic background.
DCC encodes a single-pass transmembrane receptor that mediates netrin-1-dependent axon guidance and cell migration while also acting as a dependence receptor. In the absence of netrin-1, DCC undergoes intracellular domain cleavage, leading to recruitment and activation of caspase-9, which in turn processes caspase-3 to execute apoptosis, thereby exerting tumor suppressor activity. Upon ligand binding, DCC homodimerizes and associates with UNC5 family members (UNC5A, UNC5B, UNC5C) to activate survival signaling through MAPK1/3 (ERK1/2) and promote cytoskeletal rearrangements via RhoA and Rac1. The receptor interacts with focal adhesion kinase (FAK) and Src, integrating adhesive and migratory cues. Upstream, DCC expression is regulated by the tumor suppressor p53, and epigenetic silencing through promoter methylation is frequently observed in colorectal cancers.
In the LoVo metastatic colorectal cancer setting, DCC disruption removes the pro-apoptotic dependence receptor function, permitting detailed analysis of how loss of DCC-induced apoptosis facilitates tumor cell survival and metastatic progression. This knockout cell line allows side-by-side comparison of netrin-1?Cmediated survival and migratory signaling through MAPK1/3 and Rho GTPases, clarifying the molecular determinants that shift the balance from programmed cell death to invasion.
The DCC Knockout LoVo Cell Line is amenable to a wide range of research applications. Apoptosis assays measuring caspase-9 and caspase-3 activation, together with phospho-MAPK1/3 immunoblotting and RhoA/Rac1 activity assays, enable dissection of downstream signaling events. Migration and invasion assays, co-immunoprecipitation of DCC?CUNC5 complexes, and immunofluorescence staining facilitate studies of netrin-1?Cdependent cell motility and receptor dynamics. Moreover, this line can be used in xenograft models to evaluate tumor growth and metastasis in vivo, as well as in drug screening campaigns targeting the netrin-1/DCC pathway. For technical inquiries or to request a quote, please contact Ascent Research.
