Colocalization of uPAR and α3 integrin with phospho-ERK staining in murine oral squamous cell carcinoma of the tongue (OSCC). Complex formation between uPAR and α3β1 integrin activates an ERK-dependent signal transduction pathway resulting in transcriptional regulation in OSCC cells. Tongue tumors formed following injection of cells exhibiting uPARα3β1 integrin interaction are poorly differentiated, aggressive, infiltrative lesions with perineural and vascular invasion. Using four-color immunofluorescence, colocalization of uPAR and α3 integrin is evident in murine OSCC tumors also exhibiting ERK phosphorylation, supporting the hypothesis that uPARα3β1 integrin association regulates ERK-dependent gene expression in vivo. Phospho-ERK (green), uPAR (red), α3 integrin (magenta), DAPI (blue). For further details, please see Ghosh and coworkers on page 145 in this issue.