The ACSL4 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung adenocarcinoma NCI-H1703 cell line. This loss-of-function model disrupts ACSL4 expression, enabling the study of its roles in lipid metabolism and ferroptosis. The polyclonal nature provides a heterogeneous pool of edited alleles, minimizing clonal selection artifacts. The cells were generated via CRISPR/Cas9-mediated gene disruption, resulting in functional inactivation of ACSL4 without implying specific mutation types. Researchers can use this system to investigate ACSL4-dependent mechanisms in a relevant NSCLC background.
NCI-H1703 is a human lung adenocarcinoma epithelial cell line established from a 55-year-old male patient. It serves as a standard model for non-small cell lung carcinoma (NSCLC), widely employed to study tumor biology, oncogenic signaling, and therapeutic responses. The cell line exhibits characteristic epithelial morphology and is used in drug sensitivity screens, xenograft experiments, and mechanistic studies of lung cancer progression. This background provides clinical relevance for examining ACSL4 function in lung adenocarcinoma.
ACSL4 encodes an acyl-CoA synthetase that activates long-chain polyunsaturated fatty acids, particularly arachidonic acid, to their acyl-CoA esters, promoting their incorporation into membrane phospholipids via LPCAT3. This process enriches membranes with oxidizable lipids, sensitizing cells to ferroptosis??a regulated cell death driven by lipid peroxidation. ACSL4 is transcriptionally regulated by PPAR??, SREBP1, and HIF1??, and functions downstream of EGFR and insulin signaling. Its downstream effects include lipid peroxide accumulation and eicosanoid biosynthesis. ACSL4 interacts with GPX4, ALOX12, and ALOX15, and its activity is counterbalanced by GPX4-mediated lipid peroxide reduction.
In NCI-H1703 cells, ACSL4 knockout attenuates ferroptotic death induced by erastin or RSL3, underscoring its role as a ferroptosis driver. Loss of ACSL4 may also alter lipid metabolic profiles, potentially affecting tumor growth and chemoresistance. This model therefore allows dissection of ferroptosis-associated vulnerabilities in NSCLC, offering insight into metabolic adaptation and therapy resistance mechanisms. The intersection of ACSL4 with EGFR signaling further highlights its relevance in lung cancer biology.
Applications include ferroptosis mechanism studies, cancer metabolism research, and screening for ferroptosis modulators. Typical assays encompass Western blot and RT-qPCR for ACSL4, C11-BODIPY lipid peroxidation, cell viability assays with erastin or RSL3, lipidomics by LC-MS, colony formation, xenograft tumor growth, co-immunoprecipitation with GPX4, and flow cytometry for lipid ROS. For further information, contact Ascent Research.
