Finally, the CXCL12-CXCR4 signaling axis in GEM-R PaCa cells was activated by cooperative interactions between activated GEM-R PaCa cells and stromal cells, and this activation promoted GEM-R PaCa cell proliferation, invasion and tumorigenicity. This evidence concerns the gene CXCL12 and permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.