The ACER1 Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the ACER1 gene in the NCI-H1299 lung adenocarcinoma epithelial line. This product provides a loss-of-function model for alkaline ceramidase 1, enabling studies of sphingolipid metabolism without single-cell cloning requirements. The polyclonal pool is ideal for bulk biochemical and functional analyses in a non-small cell lung cancer (NSCLC) background.
NCI-H1299 cells, derived from a lymph node metastasis of lung adenocarcinoma, are a widely used NSCLC model. The line is p53-deficient and KRAS wild-type, representing a genetic profile typical of advanced lung cancers. These epithelial cells are employed extensively in research on cancer cell proliferation, apoptosis, and drug resistance, particularly where p53-dependent signaling is compromised.
ACER1 catalyzes the hydrolysis of ceramides to sphingosine and free fatty acids, regulating the ceramide-sphingosine-1-phosphate (S1P) rheostat. Its activity is modulated by upstream factors including cellular stress signals, ceramide, S1P, retinoids, and calcium. Downstream effectors of the generated sphingosine and S1P include AMPK and protein kinase C, while ceramide-1-phosphate contributes to additional signaling. ACER1 interacts with ceramide synthases, sphingosine kinases, S1P lyase, and protein phosphatase 2A. Knockout of ACER1 disrupts ceramide catabolism, leading to ceramide accumulation and reduced sphingosine/S1P levels, thereby altering the balance between pro-apoptotic and pro-survival signals.
In p53-deficient NCI-H1299 cells, ACER1 disruption provides a system to examine ceramide-mediated apoptosis and chemosensitivity. Elevated ceramide levels may potentiate stress-induced cell death or affect responses to therapeutic agents, making this model valuable for investigating resistance mechanisms in NSCLC. The KRAS wild-type background allows dissection of RAS-independent sphingolipid signaling, potentially linking ACER1 to metabolic disorders and sphingolipidoses related to lung cancer progression.
Applications include ceramide quantification, S1P ELISA, and sphingolipidomics to profile metabolic changes, along with apoptosis and proliferation assays to assess functional outcomes. Western blotting for sphingolipid enzymes can reveal compensatory pathways, while high-throughput screening identifies ACER1 modulators. Evaluation of chemosensitivity in combination with standard therapies is another key use. For further details, contact Ascent Research.
