The HRAS Knockout Ca Ski Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Ca Ski human cervical epithelial carcinoma cell line, featuring targeted disruption of the HRAS gene. This loss-of-function model provides a heterogeneous pool of edited cells, avoiding clonal selection bias, and is optimized for functional studies of H-Ras signaling in a cancer-relevant background.
Ca Ski is an HPV16-positive cell line established from a cervical epidermoid carcinoma metastasis, widely employed in research on HPV integration and oncogenic transformation. The epithelial origin and stable expression of HPV oncoproteins make it a valuable system for exploring the role of HRAS in cervical cancer progression and the interplay between viral and host signaling pathways.
HRAS encodes H-Ras, a small GTPase that acts as a molecular switch, cycling between inactive GDP-bound and active GTP-bound states. It is activated downstream of receptor tyrosine kinases such as EGFR and FGFR, with GRB2 and SOS facilitating nucleotide exchange. Active H-Ras engages RAF1 to trigger the MAPK/ERK cascade??including MEK1/2 and ERK1/2??leading to induction of transcription factors ELK1, FOS, and JUN. Concurrently, H-Ras directly interacts with PI3K p110 to stimulate AKT/mTOR signaling, and binds RALGDS to promote alternative pathways regulating cell proliferation and survival. The cycle is modulated by RASGRF1 (GEF) and NF1 (GAP). CRISPR/Cas9-mediated disruption of HRAS eliminates these signal relays, attenuating growth factor responses.
In the context of Ca Ski cells, HRAS knockout enables researchers to dissect the specific contributions of H-Ras to cervical carcinoma phenotypes, independent of HPV16 E6/E7 activity. This model is valuable for studying dependencies on mitogenic and survival signaling, evaluating synthetic lethality, and investigating how viral oncoproteins cooperate with Ras pathways. The polyclonal format maintains cellular diversity, providing a robust system for drug sensitivity and mechanistic studies without clonal adaptation artifacts.
This product is compatible with diverse assays: Western blotting for HRAS and phospho-ERK, RT-qPCR, cell proliferation, colony formation, and wound healing assays, flow cytometry for cell cycle, soft agar assay, and xenograft tumor growth. Applications include oncogene dependency studies, functional genomics of small GTPases, drug screening (MEK, PI3K, or EGFR inhibitors), and exploration of HPV-Ras interactions. For additional information, please contact Ascent Research.
