In addition, CREB, which is a protooncogenic “master” transcription factor55,56 that promotes tumorigenesis in many cancers (i.e., non–small-cell lung carcinoma, breast cancer, acute myeloid leukemia, hepatocellular carcinoma57–60, and glioma51,52), is also tightly associated with HER2-mediated neoplastic cell growth and ROR1-mediated leukemia cell growth34,61, supporting our findings that IGFBP5 increases the phosphorylation of HER2 and ROR1 during GSC invasion. This evidence concerns the gene CREB1 and leukemia.