The GPNMB Knockout CAL-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with targeted disruption of the GPNMB gene in the human oral squamous cell carcinoma (OSCC) line CAL-27. This knockout model provides a genetically heterogeneous loss-of-function resource, preserving population-level diversity ideal for pooled screening and functional studies without clonal selection bias. The polyclonal format supports analysis of GPNMB-dependent phenotypes across a spectrum of editing events, reflecting natural tumor heterogeneity.
CAL-27 (ATCC HTB-53) originates from a tongue squamous cell carcinoma and retains wild-type p53. It is extensively characterized for rapid proliferation, invasive capacity, and anchorage-independent growth, making it a relevant host for studying OSCC invasion and metastasis. The line’s well-defined signaling network and genetic tractability facilitate rigorous dissection of gene function via CRISPR interference.
GPNMB encodes a type I transmembrane glycoprotein that promotes adhesion, migration, and invasion by binding integrin ??v??3, CD44, and EGFR. Ligation of ??v??3 activates FAK and Src kinases, which signal to ERK to upregulate MMP9 and VEGF, enhancing matrix degradation and angiogenesis. Parallel CD44-ERK and EGFR-ERK pathways amplify these effects. Upstream, GPNMB expression is induced by MITF, TGF-??, and EGF, while downstream targets include transcription factors SNAI1/SNAI2 driving EMT and CCND1 promoting proliferation. ADAM10 sheds the GPNMB ectodomain, which binds syndecan-4 on T cells to suppress immune responses, contributing to immune evasion.
In CAL-27 cells, GPNMB sustains invasive and migratory traits critical for OSCC progression. Disrupting GPNMB in this context permits direct examination of its role in tumor cell-autonomous invasion, focal adhesion turnover, and crosstalk with endothelial and immune components. Given the CAL-27 tongue origin, this model is particularly apt for investigating mechanisms governing local invasion and early metastatic dissemination in oral cancer.
This polyclonal knockout product enables applications such as Transwell migration/invasion assays to measure GPNMB-dependent motility, Western blotting for phospho-ERK and MMP9 validation, and co-immunoprecipitation to assess ??v??3 integrin interactions. Flow cytometry verifies surface GPNMB loss, while RNA-seq and tumor xenograft models reveal transcriptomic changes and in vivo growth and metastasis. It also supports pooled CRISPR screens for synthetic lethality studies. For additional information, contact Ascent Research.
