The IGFBP5 Knockout Ca Ski Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal population of Homo sapiens Ca Ski cervical carcinoma cells, carrying a targeted disruption of the IGFBP5 gene. This gene-edited pool provides a mixed population of edited cells, enabling the study of IGFBP5 loss-of-function in a genetically diverse background that better recapitulates tumor heterogeneity compared to clonal cell lines. The knockout model is designed for investigating the tumor-suppressive roles of IGFBP5 in HPV-16-positive cervical cancer, with a focus on altered insulin-like growth factor (IGF) signaling dynamics and associated downstream pathways.
Ca Ski cells are an adherent epithelial cell line established from a small intestine metastasis of a cervical carcinoma patient; they harbor integrated HPV-16 genomes and are widely employed as a model for studying molecular mechanisms of HPV-driven cervical carcinogenesis. The metastatic origin and persistent viral oncogene expression make this cell line particularly relevant for investigating invasive properties and tumor progression. In this knockout product, the Ca Ski background provides a physiologically pertinent context to examine how loss of IGFBP5 influences HPV-mediated oncogenic signaling, cell proliferation, and apoptotic responses.
IGFBP5 functions as a high-affinity IGF-binding protein that sequesters IGF-I and IGF-II, thereby attenuating IGF1R-mediated signaling. Its knockout releases free IGF ligands, leading to enhanced activation of the PI3K/Akt/mTOR and MAPK/ERK pathways through increased phosphorylation of downstream effectors such as Akt and ERK1/2. Beyond its IGF-dependent roles, IGFBP5 exerts IGF-independent effects via interactions with integrins (e.g., integrin ??v??3 and ??1) and extracellular matrix proteins, promoting apoptosis and suppressing migration through modulation of the p53 pathway. Upstream regulators including p53, TGF-??1, and E2F1 transcriptionally control IGFBP5 expression, while its downstream targets encompass cyclin D1, Bcl-2, MMP-2, MMP-9, and VEGF, linking IGFBP5 to cell cycle progression, survival, and metastasis-related processes.
In HPV-16-positive cervical carcinoma, IGFBP5 is frequently epigenetically silenced, and its loss correlates with aggressive tumor behavior. This IGFBP5 knockout Ca Ski model therefore enables dissection of the tumor-suppressive mechanisms of IGFBP5, including restraint of IGF1R-driven PI3K/Akt and MAPK/ERK signaling and p53-dependent apoptosis. The polyclonal nature allows assessment of heterogeneous gene-disruption effects on oncogenic stress responses, metabolic reprogramming, and crosstalk with HPV E6/E7 oncoproteins.
Typical experimental applications include Western blotting for phospho-Akt, phospho-ERK, and cyclin D1; RT-qPCR for IGFBP5, IGF1/2, and EMT markers; viability assays (MTT, CellTiter-Glo); Annexin V flow cytometry; Transwell migration/invasion; and ELISA for secreted IGFs. The model supports co-immunoprecipitation studies, drug response profiling with IGF1R or PI3K/Akt/mTOR pathway inhibitors, EMT and senescence research, and biomarker discovery. For further technical information, please contact Ascent Research.
