The HSDL2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the NCI-H1975 lung adenocarcinoma cell line, featuring functional disruption of the HSDL2 gene. This heterogeneous knockout pool enables investigation of HSDL2 loss-of-function effects in a non-small cell lung cancer background with EGFR L858R and T790M mutations, without clonal selection artifacts.
NCI-H1975 is an epithelial cell line derived from the pleural effusion of a 71-year-old female never-smoker diagnosed with lung adenocarcinoma. The line carries activating EGFR L858R and secondary T790M mutations, which drive constitutive kinase activity and confer resistance to first-generation EGFR tyrosine kinase inhibitors, respectively. This genetic background makes NCI-H1975 a widely used model for investigating mechanisms of targeted therapy resistance, tumor progression, and the tumor microenvironment in NSCLC.
HSDL2 is a peroxisome-localized short-chain dehydrogenase/reductase that participates in cholesterol biosynthesis and fatty acid metabolism. Its expression is transcriptionally regulated by SREBP2, placing it within the mevalonate pathway network that includes HMGCR, SQLE, and CYP51A1. HSDL2 interacts with the peroxisomal import receptor PEX5, the lipid carrier SCP2, and cofactors NAD+/NADH. In cancer, upregulated HSDL2 promotes cell proliferation and metastasis through activation of AKT and ERK signaling cascades, leading to increased levels of Cyclin D1 and matrix metalloproteinases (MMPs), which drive cell cycle progression and invasion.
In the NCI-H1975 background, loss of HSDL2 may impair the synthesis or trafficking of cholesterol and lipid metabolites essential for membrane raft formation and signaling complex assembly, potentially sensitizing EGFR-mutant cells to targeted therapies. This polyclonal knockout model enables researchers to examine whether disruption of peroxisomal lipid metabolism alters PI3K/AKT and MAPK/ERK pathway activity, reduces cholesterol-dependent clonogenic growth, or increases susceptibility to statin-induced cell death.
This product is suitable for a broad range of assays, including RT-qPCR and Western blotting for HSDL2 expression, cholesterol quantification, MTT/CCK8 proliferation assays, Transwell migration/invasion, Annexin V apoptosis, and immunofluorescence for peroxisomal localization. Global profiling approaches such as RNA-seq and phospho-signaling analysis (AKT, ERK) can map HSDL2-dependent transcriptional and signaling networks. Co-immunoprecipitation may be used to probe protein interactions. Combining the knockout with EGFR inhibitors or mevalonate pathway modulators can identify synthetic vulnerabilities. For technical support and product information, please contact Ascent Research.
