The HSDL1 Knockout NCI-H1975 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population targeting the HSDL1 gene in the human NCI-H1975 lung adenocarcinoma cell line. This CRISPR/Cas9-mediated gene disruption yields a heterogeneous loss-of-function pool, preserving genetic diversity while ensuring robust target inactivation for functional analyses.
The NCI-H1975 host cell line is a well-established non-small cell lung cancer (NSCLC) model derived from the pleural effusion of a lung adenocarcinoma patient. It harbors activating EGFR L858R and T790M mutations, conferring constitutive kinase activity and resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). This genetic profile makes it a critical system for investigating TKI resistance mechanisms and metabolic adaptations in NSCLC.
HSDL1 encodes a peroxisomal short-chain dehydrogenase/reductase that catalyzes steps in fatty acid ??-oxidation, utilizing NAD+/NADH as cofactors. Its expression is controlled by the nuclear receptors PPAR?? and PPAR?? along with the transcription factor SREBP1. Downstream, HSDL1 activity influences lipid second messenger generation and AKT signaling, a key proliferative pathway. Other essential peroxisomal components, including ACOX1, DBP, and SCP2, work together with HSDL1; disruption of HSDL1 can dysregulate peroxisomal lipid metabolism and perturb cellular lipid homeostasis.
In the NCI-H1975 context, HSDL1 knockout provides a powerful model to examine the crosstalk between peroxisomal fatty acid oxidation and EGFR-driven oncogenesis. NSCLC cells frequently reprogram lipid metabolism to sustain proliferation and develop drug resistance. Loss of HSDL1 may impair peroxisomal ??-oxidation, leading to altered lipid profiles, membrane remodeling, and modulation of AKT-mediated survival signaling. With its defined EGFR mutations, this model enables dissection of how lipid metabolic disruption impacts TKI sensitivity and supports identification of metabolic targets. The polyclonal knockout format captures population-level heterogeneity, enhancing translational relevance.
The product is intended for research on lipid metabolic reprogramming in lung adenocarcinoma, mechanisms of EGFR TKI resistance, and peroxisomal biology. Applicable assays include western blotting for lipid metabolism enzymes (e.g., ACOX1, SCP2), RT-qPCR for HSDL1 transcript levels, fatty acid oxidation assays with labeled substrates, global lipidomics by LC-MS, cell proliferation measurement under varied lipid conditions, and drug sensitivity testing with EGFR inhibitors such as osimertinib or gefitinib. For further technical inquiries, please contact Ascent Research.
