The BPGM Knockout SK-HEP-1 Polyclonal Cells product provides a heterogenous population of CRISPR/Cas9-edited cells featuring disruption of the BPGM gene in the human SK-HEP-1 liver adenocarcinoma epithelial cell line. These polyclonal knockout cells are generated through CRISPR/Cas9-mediated gene disruption, resulting in a mixed population that preserves genetic diversity while uniformly lacking functional BPGM expression. This format is well-suited for studies requiring a robust loss-of-function model without the clonal selection artifacts that can arise from single-cell-derived lines, offering a more representative mimic of heterogeneous tumor cell behavior in vitro.
The host cell line SK-HEP-1 was originally derived from the ascites of a patient with liver adenocarcinoma and is widely recognized as a model of hepatocellular carcinoma (HCC). SK-HEP-1 cells exhibit a mixed epithelial and mesenchymal phenotype, reflecting the plasticity and invasiveness observed in advanced liver cancers. Their unique characteristics make them a valuable platform for investigating tumor cell dynamics, metabolic adaptation, and the epithelial-to-mesenchymal transition (EMT) relevant to metastasis and therapeutic resistance in primary liver cancer.
BPGM encodes bisphosphoglycerate mutase, an enzyme that catalyzes the isomerization of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate (2,3-BPG) within the glycolytic pathway. This reaction diverts carbon flux away from ATP generation, instead producing 2,3-BPG, which acts as a critical allosteric regulator of hemoglobin oxygen affinity in erythrocytes. In non-erythroid cells such as hepatocytes, BPGM is implicated in modulating glycolytic flux and cellular adaptation to hypoxia. The enzyme functions as a homodimer and integrates into a glycolytic enzyme complex that includes phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase. Its expression is transcriptionally activated by KLF1 and HIF1A, and its activity is responsive to hormonal cues from insulin and glucagon, positioning BPGM at a node connecting metabolic sensing, oxygen homeostasis, and hormonal regulation.
In the context of hepatocellular carcinoma, metabolic reprogramming is a hallmark that supports rapid proliferation and survival under fluctuating oxygen and nutrient conditions. Disruption of BPGM in SK-HEP-1 cells is expected to perturb glycolytic intermediate distribution, potentially reducing 2,3-BPG levels and altering the cellular response to hypoxia. Because BPGM intersects with the HIF-1 signaling pathway, its knockout may impair HIF1A stabilization under low oxygen, thereby affecting downstream transcriptional programs involved in angiogenesis, glucose metabolism, and pH regulation. This model enables systematic dissection of 2,3-BPG functions beyond erythrocytes and provides insight into how liver cancer cells rewire central carbon metabolism to sustain malignancy.
This knockout cell pool supports a broad range of experimental applications, including metabolic profiling by LC-MS to track glycolytic and pentose phosphate pathway intermediates, Seahorse-based glycolytic flux assays to measure extracellular acidification rates, and quantitative 2,3-BPG analysis. Researchers can employ western blotting or RT-qPCR to confirm BPGM disruption and assess compensatory changes in related enzymes such as bisphosphoglycerate phosphatase. HIF1A stabilization assays under normoxia and hypoxia, combined with cell viability studies, facilitate investigation of the oxygen-sensing axis. These applications make the model suitable for studying HCC metabolic reprogramming, non-erythroid roles of 2,3-BPG, and identification of cancer metabolic targets. For further technical details and ordering information, please contact Ascent Research.
