Taken together, our data provided compelling evidence that the CXCL1/2-CXCR2 signaling pathway contributes to SCC maintenance and that during tumor progression, it becomes activated through dramatic remodeling of the Cxcl1/2 locus from a PcG-repressed to an ETS-regulated, SE-activated state. This evidence concerns the gene CXCL1 and neoplasm.