The HAVCR1 Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the Ca Ski cell line, with targeted disruption of the HAVCR1 gene encoding TIM-1. This polyclonal pool offers a heterogeneous loss-of-function model, bypassing clonal artifacts, for studying HAVCR1 functions without single-cell isolation. CRISPR/Cas9-mediated gene disruption ablates functional TIM-1 expression, enabling investigation of its roles in viral entry, immune checkpoint regulation, and signaling.
Ca Ski cells are a human epithelial cell line isolated from a cervical carcinoma metastasis, harboring an integrated HPV-16 genome. This widely used model recapitulates HPV-driven cervical carcinogenesis, epithelial barrier properties, and viral oncogene-mediated transformation, making it ideal for studying host-virus interactions and immune checkpoint involvement in cervical cancer.
HAVCR1 (TIM-1) is a type I transmembrane glycoprotein serving as a receptor for Hepatitis A virus and a co-stimulatory immune checkpoint regulator. Upstream, IL-4/STAT6 signaling and T cell receptor activation induce HAVCR1 expression. Upon engagement by phosphatidylserine, TIM-4, or HAV capsid proteins, HAVCR1 interacts with PIK3R1 to activate PI3K-AKT signaling, which regulates NFAT transcription factors and promotes production of IL-4 and IL-10. This pathway modulates immune tolerance and phagocytosis of apoptotic cells, positioning TIM-1 as a pivotal regulator of adaptive and innate immune responses.
In Ca Ski cervical carcinoma cells, HAVCR1 knockout allows dissection of TIM-1-dependent immune modulation in an HPV-positive epithelial tumor context. HPV-associated cancers often exploit immune checkpoint pathways for immune evasion; thus, loss of HAVCR1 can reveal how tumor-intrinsic TIM-1 signaling contributes to the tumor microenvironment. This model provides a platform to examine crosstalk between HPV oncoproteins and the TIM-1 pathway, potentially identifying new targets for interrupting viral persistence and malignancy.
This polyclonal knockout cell product supports functional studies of HAVCR1 in viral recognition, cytokine secretion, and apoptosis. Typical assays include RT-qPCR and Western blot for confirming gene disruption, flow cytometry and immunofluorescence for protein expression, and functional readouts such as proliferation, apoptosis, and cytokine profiling. Phospho-AKT analysis can assess downstream signaling, while co-immunoprecipitation and reporter assays map altered interaction networks. Researchers can screen HAVCR1 inhibitors or study epithelial-immune cell communication. For further information, please contact Ascent Research.
