The CASP6 Knockout LoVo Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population targeting the CASP6 gene in the LoVo colorectal adenocarcinoma cell line. This loss-of-function model provides a heterogeneous pool of gene-edited cells, enabling robust functional studies of caspase-6 without clonal selection biases. The polyclonal format maintains natural cellular diversity while eliminating CASP6 expression, making it suitable for apoptosis signaling, drug response profiling, and substrate cleavage analyses.
LoVo cells are an epithelial colorectal adenocarcinoma line derived from a metastatic lymph node of a Dukes?? type C patient. This cell line is widely used as a model for metastatic colorectal cancer, offering a clinically relevant platform to study tumor biology and therapeutic resistance. Combining the CASP6 knockout with the LoVo background enables focused investigation of caspase-6-dependent processes in colorectal cancer progression and apoptosis regulation.
CASP6 encodes caspase-6, an executioner caspase activated downstream of initiator caspases caspase-8 and -9 during intrinsic and extrinsic apoptosis. Active caspase-6 cleaves lamin A/C, PARP1, and alpha-tubulin, driving nuclear fragmentation and cytoskeletal disassembly. It also processes huntingtin and amyloid precursor protein, contributing to neurodegenerative pathology. Caspase-6 activity is regulated by XIAP and cIAP1/2, with relief from cytochrome c/SMAC-mediated apoptosis. The protease functions within a network containing APAF1, caspase-9, caspase-3, and BCL-2 family members, integrating apoptotic signals into an irreversible proteolytic cascade.
In the LoVo colorectal cancer context, CASP6 knockout allows dissection of apoptosis resistance mechanisms that arise during tumor progression and therapy. Loss of caspase-6 may impair executioner function, altering sensitivity to chemotherapeutics, and its role in cleaving lamin A/C connects to cellular migration and invasion, key metastatic processes. These cells also serve as a versatile system to study caspase-6 substrate specificity and the consequences of impaired cleavage of neurodegeneration-related proteins, leveraging conserved enzymatic recognition motifs outside a neuronal background.
These polyclonal knockout cells support a range of assays including Western blotting for cleaved caspase-6, lamin A/C, and PARP1; caspase-6 activity assays; Annexin V/PI flow cytometry; MTT viability tests; and transwell migration/invasion studies. RNA-seq transcriptome profiling can uncover gene expression changes, while the cells facilitate small molecule screening and novel substrate identification via proteomics. For additional information or customized models, contact Ascent Research.
