The INSR Knockout Ca Ski Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population targeting the insulin receptor (INSR) gene. This loss-of-function model provides a versatile tool for investigating insulin signaling disruptions in a human cervical carcinoma background. The polyclonal population retains genetic heterogeneity, enabling robust and reproducible studies of INSR-mediated pathways without clone-specific artifacts.
The host Ca Ski cell line is a human cervical epidermoid carcinoma line derived from a metastatic site and is characterized by integrated HPV16 genome. These cells serve as an established in vitro model for HPV16-positive cervical cancer, exhibiting oncogenic features driven by viral E6 and E7 proteins. The Ca Ski line is widely used to study HPV-associated carcinogenesis, host-virus interactions, and therapeutic interventions.
INSR encodes a receptor tyrosine kinase that, upon binding insulin, IGF1, or IGF2, undergoes autophosphorylation and activates downstream signaling cascades. The receptor recruits adaptor proteins such as IRS1 and SHC, leading to activation of PI3K/AKT and MAPK/ERK pathways. Upstream regulators include PTP1B and TNF-alpha, while downstream effectors encompass AKT, mTOR, FOXO1, SREBP1c, and GLUT4. Interacting factors like IRS2, GRB2, SOS, and the PI3K p85 subunit form critical nodes in signal transduction. The INSR-IRS1-PI3K-AKT axis promotes metabolic responses and cell survival, whereas INSR-SHC-GRB2-SOS-RAS-RAF-MEK-ERK signaling governs proliferation and differentiation. Disruption of INSR abrogates these insulin-mediated networks.
In the Ca Ski context, INSR knockout impairs insulin-driven signaling, potentially affecting HPV16-positive cervical cancer cell metabolism, growth, and survival. This model enables dissection of INSR-dependent contributions to oncogenic processes, including metabolic reprogramming, resistance to apoptosis, and cross-talk with HPV oncoproteins. Researchers can explore how loss of insulin receptor function influences tumor behavior and response to metabolic stress.
These polyclonal knockout cells are suitable for studying insulin signaling, cancer metabolism, and insulin resistance mechanisms in HPV-related cancers. Typical applications include drug screening for insulin sensitizers, functional analyses via Western blotting of INSR and phospho-AKT, RT-qPCR for GLUT4 and FOXO1, glucose uptake assays, cell proliferation (MTT) assays, flow cytometry for cell cycle and apoptosis, and migration/invasion assessments. The model supports investigations into crosstalk between insulin pathways and HPV oncogenes. For further inquiries, please contact Ascent Research.
