This product offers a CRISPR/Cas9-edited polyclonal knockout cell population targeting the JAK2 gene in the human Ca Ski cervical carcinoma cell line. The polyclonal format provides a heterogeneous pool of gene-disrupted cells, avoiding clonal artifacts and enabling robust pooled analyses of JAK2 function. This loss-of-function model is designed for investigating JAK2-mediated signaling pathways in a disease-relevant context.
The Ca Ski cell line was established from a metastasis of a cervical carcinoma located in the small intestine mesentery and contains integrated HPV-16 DNA. As an adherent epithelial line, it serves as a key model for studying HPV-driven oncogenesis, including the interplay between viral oncoproteins and host signaling networks governing proliferation, apoptosis, and metastatic progression.
JAK2 encodes a non-receptor tyrosine kinase that acts as a critical signaling node downstream of cytokine receptors. Upon ligand binding (e.g., IL-6 to GP130, EPO to EPOR, TPO to TPOR, GH to GHR), JAK2 becomes activated, undergoes trans-phosphorylation, and phosphorylates cytoplasmic receptor tyrosine residues. This recruits STAT transcription factors??primarily STAT3, STAT5A, and STAT5B??which are then phosphorylated by JAK2, dimerize, and enter the nucleus to induce target genes such as CCND1, BCL2L1, SOCS, and MYC. Negative regulation is exerted by SOCS1, SOCS3, and the phosphatase SHP-1. Additionally, JAK2 integrates signals into the PI3K-AKT and RAS-MAPK cascades through adaptor proteins, thereby modulating cell survival, proliferation, and metabolic programs.
In cervical carcinoma, especially HPV-16-positive tumors, the JAK-STAT pathway is frequently dysregulated and contributes to oncogenic transformation by sustaining proliferative signaling and resisting apoptosis. The Ca Ski cell line, with its defined HPV background, provides an ideal platform to interrogate the specific role of JAK2 in this context. By disrupting JAK2 in these cells, researchers can assess the consequences on cell cycle progression, survival, and invasive behavior, as well as potential synthetic lethal interactions with HPV oncoproteins. This polyclonal knockout population permits the study of JAK2 dependency without clonal bias, offering insights into pathway addiction and therapeutic targets.
Experimental workflows may include western blotting for JAK2 and phospho-STAT3/5, RT-qPCR quantification of transcriptional targets (e.g., CCND1, BCL2L1), and cytokine stimulation assays monitored by phospho-flow cytometry. Phenotypic analyses can be performed using MTT or BrdU proliferation assays, caspase-3 activation apoptosis assays, transwell migration/invasion assays, and colony formation assays. The model is also compatible with drug sensitivity profiling using JAK inhibitors like ruxolitinib, enabling preclinical evaluation of targeted therapies. For technical inquiries, please contact Ascent Research.
