The CD38 Knockout Ca Ski Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal population with targeted disruption of the CD38 gene in the Ca Ski cervical carcinoma epithelial cell line. This polyclonal knockout model is designed for loss-of-function studies, offering a heterogeneous cell pool that mimics the genetic variability found in tumor environments. It is intended for research into CD38-dependent processes such as calcium signaling, NAD+ metabolism, and cell adhesion within oncology and immunology contexts.
Ca Ski cells are derived from a human cervical squamous cell carcinoma and contain an integrated HPV-16 genome, making them a classic model for HPV-driven cervical cancer. These epithelial cells retain key oncogenic pathways driven by HPV E6 and E7 oncoproteins, which disrupt p53 and Rb tumor suppressors. This genetic background facilitates investigations into the interplay between HPV oncogenesis and CD38-regulated pathways, particularly how ectoenzyme-driven NAD+ hydrolysis and calcium mobilization influence malignant properties such as proliferation and immune evasion.
CD38 functions as a multifunctional ectoenzyme that hydrolyzes NAD+ to cyclic ADP-ribose (cADPR), a second messenger that triggers calcium release from intracellular stores via ryanodine receptors. Its activity is transcriptionally regulated by STAT3, NF-??B, and retinoic acid, and is stimulated by cytokines such as IL-2 and IL-4. Downstream, cADPR also modulates TRPM2 channels and ERK1/2 signaling, while CD38 forms complexes with CD31/PECAM-1 and caveolin-1 to influence cell adhesion. Through these interactions, CD38 integrates metabolic and immune signals, controlling processes like proliferation, migration, and apoptosis.
In the Ca Ski cervical carcinoma context, CD38 knockout provides insights into how loss of CD38-dependent calcium and NAD+ signaling impacts HPV-transformed cells. Disruption of CD38 may alter mitochondrial metabolism, oxidative stress responses, and adhesion profiles, potentially affecting tumor growth and immune interactions. The polyclonal nature of the knockout recapitulates the heterogeneity observed in solid tumors, making it suitable for studies of drug sensitivity and resistance mechanisms related to NAD+-consuming pathways.
This knockout model is applicable in calcium flux assays using dyes such as Fluo-4, NAD+ quantification via enzymatic cycling, and flow cytometry for CD38 surface loss verification. Additional assays include migration and proliferation studies, apoptosis detection, and immunoblotting to assess downstream effectors like ERK1/2 phosphorylation. These cells enable mechanistic studies linking CD38 activity to HPV-driven cervical cancer progression. For further details, please contact Ascent Research.
