The ACSL4 Knockout PaTu 8988t Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the human pancreatic ductal adenocarcinoma cell line PaTu 8988t, featuring targeted disruption of the ACSL4 gene. This product provides a heterogeneous pool of gene-edited cells without clonal isolation, enabling loss-of-function studies in a population context that avoids clonal artifacts.
The parental PaTu 8988t cell line was established from a liver metastasis of a pancreatic adenocarcinoma and harbors pathogenic KRAS and TP53 mutations, two hallmark genetic lesions in aggressive pancreatic ductal adenocarcinoma. This genetic background drives prominent metabolic reprogramming and invasive properties, making it a clinically relevant model for investigating lipid metabolism and regulated cell death pathways in metastatic pancreatic cancer.
ACSL4 encodes an acyl-CoA synthetase that activates long-chain polyunsaturated fatty acids (PUFAs) such as arachidonic acid by converting them into acyl-CoA esters. This step is required for PUFA incorporation into membrane phospholipids by LPCAT3, producing phosphatidylethanolamine species (PE-PUFAs) that are substrates for oxidation by ALOX15 and other lipoxygenases. ACSL4 is transcriptionally controlled by SREBP1 and PPAR?? and is functionally opposed by the GPX4/SLC7A11 antioxidant axis. It directly interacts with LPCAT3, POR, and ACSL1, placing ACSL4 at a critical intersection of lipid metabolism and ferroptotic death signaling.
In the KRAS/TP53-mutant PaTu 8988t background, ACSL4 disruption abrogates PUFA-CoA production, thereby blocking the synthesis of oxidation-prone phospholipids and conferring resistance to ferroptosis induced by GPX4 inhibitors (e.g., RSL3) or system xc? inhibitors (e.g., erastin). This polyclonal knockout model thus allows precise investigation of how lipid peroxidation-dependent cell death contributes to pancreatic tumor biology, drug sensitivity, and metastatic potential within a genetically defined cancer context.
Researchers can apply these polyclonal ACSL4 knockout cells in diverse assays, including cell viability measurements with ferroptosis inducers erastin and RSL3, C11-BODIPY-based lipid peroxidation detection, and flow cytometry for cell death quantification. Additional applications encompass phospholipidomics and lipidomics profiling to dissect membrane remodeling, colony formation and wound healing migration assays for tumorigenic and metastatic readouts, and RNA sequencing to explore ACSL4-dependent transcriptional networks. These cells are also suitable for pooled drug sensitivity screens to identify novel ferroptosis-targeting agents. For further technical details or customization options, please contact Ascent Research.
