The ACER1 Knockout HCT 116 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HCT 116 human colorectal carcinoma cell line. Through targeted disruption of the ACER1 gene, this model enables in-depth investigation of alkaline ceramidase 1 function in sphingolipid metabolism and its influence on cell fate decisions. The polyclonal format provides a genetically diverse population with widespread gene disruption, suitable for studying collective cellular responses.
HCT 116 is a widely studied KRAS-mutant colorectal adenocarcinoma line characterized by microsatellite instability (MSI-H), which leads to a hypermutable phenotype and potent oncogenic signaling through elevated ERK and AKT activity. This background provides a clinically relevant context for exploring sphingolipid-mediated processes in colorectal cancer.
ACER1 encodes an endoplasmic reticulum-resident alkaline ceramidase that catalyzes ceramide hydrolysis to yield sphingosine, a pivotal reaction in sphingolipid metabolism. Its transcription is upregulated by p53 and TNF??, integrating this enzyme into apoptotic and stress signaling networks. Sphingosine serves as a substrate for sphingosine kinases SPHK1 and SPHK2, which produce sphingosine-1-phosphate (S1P), a bioactive lipid that engages five G protein-coupled receptors (S1PR1-5). Downstream, S1P signaling activates AKT, ERK, and NF??B cascades to promote survival, proliferation, and migration. Concurrently, ceramide synthases generate ceramide, whose levels are counterbalanced by ACER1 activity.
Disruption of ACER1 in HCT 116 cells decouples this balance, causing ceramide accumulation and diminished S1P. This metabolic alteration enhances ceramide-induced apoptosis while suppressing S1P-dependent survival and proliferation signals that are otherwise amplified by mutant KRAS. The interplay between ceramide and S1P is particularly critical in KRAS-mutant contexts, where apoptotic resistance and metastatic potential are key disease drivers. The knockout model thus enables dissection of how the ceramide/S1P axis controls colorectal cancer cell apoptosis, migration, and drug responsiveness.
This polyclonal knockout cell population is suited for studies of ceramide-mediated apoptosis in colorectal carcinoma, analysis of sphingolipid metabolism in tumorigenesis, pharmacological screening of ceramide pathway therapeutics, and investigations into drug resistance mechanisms. Compatible assay formats include Western blotting for key signaling proteins, LC-MS-based sphingolipid profiling, Annexin V apoptosis quantification, cell viability measurements, Transwell migration assays, and S1P ELISA. For further inquiries and ordering, please contact Ascent Research.
