In Stock Cell Lines
Homo sapiens (Human)
Bone
Adherent
The HCAR1 Knockout U2OS Cell Line is a CRISPR/Cas9-edited loss-of-function model targeting the lactate receptor GPR81/HCAR1 in human osteosarcoma cells. This knockout cell line abolishes HCAR1-mediated signaling, including cAMP suppression and downstream PKA/HSL pathways, enabling precise dissection of lactate effects in cancer and metabolism. Derived from the U2OS bone cancer cell line, this product is ideal for studying tumor microenvironment interactions, metabolic regulation, and drug screening. Key applications include cAMP assays, lipolysis analysis, and migration studies, facilitated by the stable knockout of the Gi/o-coupled receptor.
CHEK2 Knockout K562 Polyclonal Cells
Cat. No. ARG19255
STC2 Knockout HEK293T Cell Line
Cat. No. ARG44135
OCLN Knockout DLD-1 Polyclonal Cells
Cat. No. ARG12045
EDC3 Knockout AGS Polyclonal Cells
Cat. No. ARG40428
CTSC Knockout HCT116 Polyclonal Cells
Cat. No. ARG7194
NDST3 Knockout HEK293T Polyclonal Cells
Cat. No. ARG3753
The HCAR1 Knockout U2OS Cell Line is a CRISPR/Cas9-edited knockout cell line that eliminates functional expression of the human HCAR1 (Hydroxycarboxylic Acid Receptor 1) gene. This engineered model provides a loss-of-function background for dissecting HCAR1-mediated signaling in a human osteosarcoma system. Generated via CRISPR/Cas9-mediated gene disruption in the U2OS cell line, it offers a stable resource for reproducible experimentation in metabolism and cancer research.
The parental U2OS cell line is a human bone osteosarcoma epithelial cell line originally isolated from a 15-year-old female. Characterized by malignant osteoblast properties, U2OS cells are extensively used in studies of bone cancer biology, metabolic adaptations, and cellular signaling. High glycolytic flux in the tumor microenvironment elevates extracellular lactate, potentially engaging HCAR1. Thus, this knockout in U2OS cells provides a physiologically pertinent platform to examine lactate receptor functions.
HCAR1, also termed GPR81, is a cell-surface GPCR selectively activated by the endogenous metabolite lactate. Upon ligand binding, HCAR1 couples to Gi/o proteins to inhibit adenylyl cyclase, lowering intracellular cAMP and attenuating PKA activity. This signaling axis suppresses lipolysis in adipocytes by decreasing PKA-dependent phosphorylation of hormone-sensitive lipase (HSL) and perilipin. Downstream, HCAR1 signaling modulates ERK1/2 and the transcription factor SREBP-1c, linking lactate to energy homeostasis. Receptor regulation involves ??-arrestin-2 and GRK2, and activation can be mimicked by the synthetic agonist 3,5-dihydroxybenzoic acid.
In osteosarcoma, lactate produced via the Warburg effect accumulates in the tumor microenvironment and may act through HCAR1 to mediate metabolic adaptation, migration, or survival signals. The HCAR1 knockout U2OS line permits dissection of these lactate-triggered responses from its metabolic substrate role. This model is especially relevant for probing crosstalk between lactate signaling and oncogenic pathways in bone cancer, potentially revealing new therapeutic vulnerabilities.
This cell line is designed for diverse research applications. It enables cAMP assays to quantify lactate-mediated signaling changes, western blotting for phospho-ERK1/2 and HSL to monitor downstream paths, and glycerol release assays to measure lipolysis. Metabolic flux analysis and lactate uptake experiments can delineate metabolic rewiring upon HCAR1 loss. Additionally, cell migration assays and drug screening for HCAR1 modulators are supported. For further details or to discuss custom projects, please contact Ascent Research.
