The ACER1 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed for functional studies of alkaline ceramidase 1. This product consists of a heterogeneous pool of Ca Ski cells in which the ACER1 locus has been disrupted via CRISPR/Cas9-mediated gene editing, providing a loss-of-function model suitable for population-based assays without single-cell cloning artifacts.
The parental Ca Ski cell line is a human cervical epithelial carcinoma model established from an epidermoid cervical carcinoma. These cells are positive for integrated human papillomavirus type 16 (HPV-16) DNA and constitutively express the viral E6 and E7 oncoproteins, which target p53 and pRb, respectively. Ca Ski cells are widely used to study HPV-driven carcinogenesis, tumor cell migration, and therapeutic responses in cervical cancer.
ACER1 encodes an alkaline ceramidase that hydrolyzes long-chain ceramides into sphingosine and free fatty acids, a key regulatory step in sphingolipid metabolism. The enzyme controls the balance between pro-apoptotic ceramide and sphingosine-1-phosphate (S1P), a potent bioactive lipid that signals through five G protein-coupled receptors (S1PR1-5). ACER1 expression is regulated by TP53, AP-1 transcription factors, calcium, phorbol esters, and retinoids. Downstream, ACER1-derived sphingosine serves as substrate for sphingosine kinases SPHK1/2 to produce S1P, which activates protein kinase C (PKC) and other effectors. The enzyme interacts with ceramide synthases (CERS1-6) and SPHK1 within the sphingolipid metabolic network. Disruption of ACER1 therefore shifts the ceramide/S1P rheostat, with potential impacts on apoptosis, proliferation, and migration.
In the HPV-16-positive cervical carcinoma background of Ca Ski cells, ACER1 knockout offers a platform to investigate how sphingolipid metabolic alterations intersect with viral oncogenesis. Loss of ceramidase activity may elevate ceramide levels and reduce S1P production, potentially sensitizing cells to ceramide-mediated apoptosis while attenuating S1P-driven survival and invasive signals. This model enables dissection of the role of sphingolipid signaling in HPV-associated tumor progression, as well as identification of sphingolipid-dependent vulnerabilities in cervical cancer.
Typical experimental applications include lipidomic profiling by LC-MS to quantify ceramide, sphingosine, and S1P; apoptosis assessment via Annexin V/PI; proliferation analysis using MTS; migration and invasion assays in transwell chambers; cell cycle analysis by flow cytometry; and transcriptomic studies through RT-qPCR or RNA-seq. The knockout cells are suitable for screening ACER1-modulating small molecules and investigating crosstalk with retinoid and phorbol ester pathways. Owing to ACER1??s role in epidermal ceramide metabolism, they may also serve as a model for skin barrier dysfunction research. For further details or order inquiries, contact Ascent Research.
