The HSDL2 Knockout SK-HEP-1 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal cell population derived from the SK-HEP-1 human hepatic adenocarcinoma cell line, carrying targeted disruptions in the HSDL2 gene. This pooled knockout model offers a heterogeneous loss-of-function system for investigating HSDL2-mediated processes in a liver cancer background. The polyclonal format provides a practical balance between knockout efficiency and population-level reproducibility, suitable for a broad range of biochemical and functional studies.
SK-HEP-1 cells were originally isolated from the ascites of a patient with liver adenocarcinoma and have since been widely employed as a model for hepatic cancer and metabolic interactions. These cells exhibit an epithelial phenotype and retain key characteristics of transformed hepatocytes, including active lipid and cholesterol metabolism pathways. Their derivation from a metastatic source makes them particularly valuable for studying the intersection of oncogenic signaling and metabolic reprogramming, serving as an appropriate host for HSDL2 disruption studies.
HSDL2 encodes a hydroxysteroid dehydrogenase-like enzyme that participates in cholesterol metabolism and steroid biosynthesis. Upstream, its expression is regulated by sterol-regulatory element-binding proteins (SREBP1/2), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). HSDL2 functionally interacts with SOAT1, CYP51A1, and NSDHL and influences downstream effectors including cholesterol esters, oxysterols, and low-density lipoprotein receptor (LDLR) expression. Disruption of HSDL2 impinges on the SREBP2?CHMGCR?CLDLR axis and alters cholesterol-sensitive signaling through LXR and ABCA1, thereby perturbing lipid raft integrity and related membrane-associated processes.
In the SK-HEP-1 background, HSDL2 knockout disrupts cholesterol homeostasis and creates an experimental system to dissect the contribution of sterol metabolism to cancer cell proliferation, survival, and drug susceptibility. Given the relevance of cholesterol to membrane biology and signaling platform formation, this model enables interrogation of how altered cholesterol distribution impacts oncogenic pathways. It is well suited to exploring connections between metabolic syndrome?Cassociated hypercholesterolemia and hepatic tumorigenesis, as well as to probing adaptive responses to cholesterol deprivation in a cancer context.
Typical applications include cholesterol homeostasis studies, lipid metabolism research, and cancer metabolism investigations, with a particular focus on drug resistance mechanisms that rely on membrane lipid remodeling. Standard analytical approaches include Western blotting and RT-qPCR for HSDL2 expression, cholesterol quantification assays, filipin staining for free cholesterol localization, LC?MS-based lipidomics to profile sterol intermediates, Seahorse metabolic flux analysis, RNA-sequencing, and cell viability assays under lipid-depleted conditions. These readouts facilitate robust phenotypic and molecular characterization of the knockout model. For additional product information, please contact Ascent Research.
