For example, cancer-associated fibroblasts (CAFs), in breast-cancer stroma, produce CXCL12 and IGF-1, which select Src hyperactive cancer clones, and promote bone metastases [157,158]; in NSCLC, stimuli from CAFs in the tumor microenvironment could dictate de novo creation of the CD133+CXCR4+ CSCs subset, directly linked to EMT induction with the acquisition of increased dissemination [20]. This evidence concerns the gene CXCR4 and breast cancer.