ACER1 Knockout LoVo Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the LoVo human colorectal adenocarcinoma cell line, in which targeted gene disruptions have been introduced into the ACER1 locus. This polyclonal product provides a pooled population of cells carrying heterogeneous ACER1 loss-of-function mutations, enabling functional studies of alkaline ceramidase 1 without the constraints of clonal selection. The knockout model is suitable for dissecting sphingolipid-mediated signaling events in a well-characterized metastatic cancer background.
The LoVo host cell line was originally established from a metastatic lymph node of a 56-year-old Caucasian male with colon adenocarcinoma. LoVo cells exhibit an epithelial morphology, are tumorigenic in nude mice, and harbor oncogenic mutations including KRAS G13D, APC, and TP53. These genetic alterations render LoVo cells a clinically relevant model of aggressive colorectal adenocarcinoma, widely employed in cancer biology and drug discovery research.
The ACER1 gene encodes alkaline ceramidase 1, an enzyme that hydrolyzes very long chain ceramides to yield sphingosine and free fatty acids, thereby diminishing intracellular pro-apoptotic ceramide species and generating substrate for sphingosine-1-phosphate (S1P) production. ACER1 is transcriptionally regulated by TP53 (p53) in response to DNA damage and genotoxic stress. The sphingosine product is subsequently phosphorylated by sphingosine kinase 1 (SPHK1) to form S1P, a bioactive lipid that signals through five G-protein-coupled receptors (S1PR1?C5) to activate downstream effectors including AKT and MAPK pathways. ACER1 thus functions at a pivotal node in the sphingolipid rheostat, modulating the equilibrium between ceramide-driven apoptosis and S1P-dependent survival and proliferation.
Within the LoVo colorectal adenocarcinoma background, which bears mutant TP53 and oncogenic KRAS, disruption of ACER1 is anticipated to perturb sphingolipid homeostasis, altering the balance of ceramide and sphingosine species. This dysregulation can impact ceramide-mediated apoptotic signaling and S1P-driven AKT/MAPK pathway activity, potentially influencing key tumorigenic properties such as cell proliferation, migration, and apoptotic resistance. Consequently, these polyclonal knockout cells provide a tractable system to explore how loss of alkaline ceramidase function cooperates with established colorectal driver mutations to modulate disease progression.
These polyclonal ACER1 knockout cells are designed for a broad spectrum of research applications, including Western blotting and RT?qPCR to verify gene disruption, mass spectrometry-based sphingolipid profiling to quantify changes in ceramide and sphingosine pools, and functional apoptosis assays using Annexin V/propidium iodide staining or caspase-3/7 activity measurements. Additional uses encompass cell proliferation analyses (MTS assay), Transwell migration experiments, and immunofluorescence localization of ceramide species, enabling comprehensive investigation of sphingolipid dynamics in colorectal cancer. For further information, please contact Ascent Research.
