The HACL1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population for loss-of-function studies of HACL1 in human lung adenocarcinoma. This product offers a genetically disrupted pool of NCI-H1975 cells, eliminating the need for clonal isolation and enabling pooled screening applications. The polyclonal format retains heterogeneity while ensuring effective target disruption, providing a robust model for investigating peroxisomal ??-oxidation.
NCI-H1975 is an EGFR L858R/T790M mutant non-small cell lung adenocarcinoma cell line widely used in oncology research. It serves as a model for targeted therapy resistance and EGFR-driven tumor progression. This host provides a disease-relevant background to study the interplay between oncogenic signaling and peroxisomal lipid metabolism.
HACL1 encodes 2-hydroxyacyl-CoA lyase 1, which catalyzes the peroxisomal cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA??the key step in ??-oxidation. This pathway degrades phytanic acid, a branched-chain lipid implicated in Refsum disease. Upstream, HACL1 is regulated by PPAR-alpha and phytanic acid, and acts downstream of PHYH. Its products feed into ??-oxidation via AMACR and ACOX1. HACL1 interacts with PEX5 for peroxisomal import. Loss of HACL1 disrupts phytanic acid breakdown, causing toxic accumulation and metabolic imbalance.
In NCI-H1975 cells, HACL1 knockout enables dissection of ??-oxidation’s role in cancer lipid metabolism. EGFR mutations often drive metabolic reprogramming, and HACL1 may modulate phytanic acid-derived lipids affecting signaling or survival. This model allows assessment of whether ??-oxidation supports tumor cell fitness under stress or influences EGFR inhibitor sensitivity.
Applications include phytanic acid toxicity assays, GC-MS quantification, and HACL1 activity measurements. Researchers can verify knockout via western blot and RT-qPCR, assess peroxisomal markers by immunofluorescence, and perform lipidomics to track ??-oxidation intermediates. The model supports Refsum disease research, peroxisomal biogenesis disorder studies, and cancer metabolism screening. PPAR-alpha agonist effects on lipid catabolism can also be evaluated. For further information, contact Ascent Research.
