The H6PD Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the human Ca Ski cervical carcinoma line, engineered for targeted disruption of the H6PD gene. This heterogeneous knockout model enables loss-of-function studies without clonal isolation. By eliminating H6PD expression, the product provides a tool to investigate endoplasmic reticulum (ER) NADPH generation and glucocorticoid metabolism in a cancer-relevant background.
The Ca Ski host cell line originates from an epidermoid cervical carcinoma and is positive for human papillomavirus type 16 (HPV-16), making it a widely used model for cervical cancer research. These epithelial cells retain key oncogenic features and are extensively employed to study viral oncogene effects, tumor biology, and therapeutic responses. This background provides a relevant epithelial context for exploring H6PD-associated metabolic pathways.
H6PD encodes hexose-6-phosphate dehydrogenase, an ER lumenal enzyme that generates NADPH via the pentose phosphate pathway. This NADPH pool is an obligate cofactor for 11??-hydroxysteroid dehydrogenase type 1 (11??-HSD1), which catalyzes the conversion of cortisone to active cortisol, thereby regulating local glucocorticoid activation and downstream glucocorticoid receptor (GR) signaling. H6PD is modulated by upstream factors including XBP1s, insulin, glucose, and glucocorticoids, and it interacts with NADP+/NADPH and ER oxidoreductases. Its disruption consequently impacts 11??-HSD1 activity, cortisol production, and ER redox-sensitive protein function.
In the Ca Ski context, H6PD knockout enables dissection of the crosstalk between ER redox homeostasis, glucocorticoid metabolism, and cervical cancer biology. Loss of H6PD impairs NADPH supply to 11??-HSD1, providing a model to study consequences similar to cortisone reductase deficiency and metabolic dysregulation seen in obesity and type 2 diabetes. This system is particularly valuable for investigating how glucocorticoid signaling influences HPV-positive tumor cell behavior, including proliferation and stress responses.
Applications include glucocorticoid metabolism studies, metabolic disease modeling, ER redox biology, and screening of 11??-HSD1 inhibitors. Typical assays involve cortisol/cortisone LC-MS, 11??-HSD1 activity assays, NADPH/NADP+ ratio measurements, western blotting, RT-qPCR, cell proliferation assays, and drug sensitivity testing. For further information, please contact Ascent Research.
