ACER1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human gastric adenocarcinoma cell line AGS. This loss-of-function model is generated by CRISPR/Cas9-mediated disruption of the ACER1 gene, which encodes alkaline ceramidase 1. The polyclonal format provides a heterogeneous pool of edited cells, each harboring targeted gene disruptions, enabling robust functional studies without clonal selection. This product is intended for researchers investigating sphingolipid metabolism and ceramide signaling in the context of gastric cancer.
The parental AGS cell line is a widely used model of human gastric adenocarcinoma, established from a poorly differentiated gastric tumor of a 54-year-old female patient. These epithelial cells retain key characteristics of gastric cancer, including aggressive growth behavior and active signaling pathways relevant to tumor biology. AGS cells are commonly employed to study gastric cancer cell proliferation, apoptosis, migration, and drug responses, making them a suitable host for interrogating the tumor-suppressive or oncogenic roles of sphingolipid-modifying enzymes.
ACER1 is an endoplasmic reticulum-resident alkaline ceramidase that catalyzes the hydrolysis of ceramides to yield sphingosine and free fatty acid, representing a critical regulatory step in the sphingolipid pathway. Its activity is modulated by upstream signals including TNF-alpha, PKC-alpha, p53, and NF-kB. Following ACER1-mediated conversion, sphingosine can be phosphorylated by sphingosine kinase 1 (SPHK1) to produce sphingosine-1-phosphate (S1P), a bioactive lipid that signals through S1P receptors (S1PR1?C5) to promote cell survival and proliferation via AKT and JNK pathways. Conversely, accumulated ceramides interact with Bcl-2 family proteins and cathepsin D to execute apoptosis. Thus, ACER1 sits at a signaling hub that balances ceramide-induced cell death and S1P-mediated survival.
In the AGS gastric cancer model, loss of ACER1 function profoundly alters this balance. Ceramide accumulation due to disrupted hydrolysis triggers heightened apoptotic signaling and anti-proliferative effects, while decreased sphingosine and S1P levels attenuate pro-survival and pro-inflammatory cascades. This phenotype mirrors potential tumor-suppressive mechanisms, making the ACER1 knockout cells a valuable tool for dissecting how ceramide/sphingosine rheostat dysfunction contributes to gastric adenocarcinoma progression, chemoresistance, and inflammatory responses. Researchers can use these cells to evaluate the impact of ACER1 deficiency on tumor cell fitness and to explore compensatory activation of alternative ceramide-metabolizing enzymes.
Typical applications include quantitative sphingolipid profiling by mass spectrometry to monitor ceramide species and S1P levels, Western blotting and RT-qPCR to assess expression of pathway components (e.g., SPHK1, Bcl-2, cathepsin D), and functional assays such as annexin V apoptosis detection, MTT proliferation assays, and migration/invasion studies. Additionally, these cells are suitable for sphingosine kinase activity measurements, S1P ELISA, and immunofluorescence-based localization studies. High-throughput screening of ceramide pathway modulators or candidate therapeutics in this isogenic background can reveal ACER1-dependent drug sensitivities. For further details and ordering information, please contact Ascent Research.
