Correspondingly, our murine model demonstrated that silencing AKT2 decreased metastasis to the liver and formation of secondary lesions in comparison to mice injected with control neuroblastoma cells with high endogenous expression of AKT2. The oncogenic role of AKT2 demonstrated in this study may provide a possible explanation as to why AKT activation has been shown to be a predictor of poor outcome in patients with neuroblastoma. In summary, our findings further support the notion that GRP/ GRP-R is a promising therapeutic target in the treatment of clinically aggressive neuroblastomas. Moreover, GRP-R modulates N-myc expression in neuroblastoma cells by AKT2 isoform, but not the AKT1 or AKT3. Targeting GRP/GRP-R/AKT2 would be advantageous in developing a novel therapeutic option for aggressive and undifferentiated neuroblastomas with a high propensity for metastasis. Loss-of function mutations in CLMP were found in CSBS patients. These patients have a congenital short small intestine with a mean length of 50 cm compared to a normal length of 250 cm at birth. CLMP is a trans-membrane protein and colocalizes with the tight junction proteins ZO-1 and occluding. Immunostaining on human embryos showed that CLMP was expressed in many tissues including the gut. Knock down experiments of the The tubs were placed at a common shelf height in a completely randomized design at the JARTU laborator orthologue in zebrafish resulted in general developmental defects including an affected intestine. Goblet cells are normally present in the mid intestine in zebrafish, and can therefore be used as a marker for this epithelial tissue. Since the goblet cells were absent in the morphant zebrafish, knock down of the orthologue of CLMP in zebrafish would probably result in the absence of the small intestine. All these findings suggest that CLMP has an important role in intestinal development, although its function is still largely unclear. However, it is known that transient transfection of human CLMP into human intestinal epithelial T84 cells showed CLMP localization at the cell-cell membrane contacts. It is also known that CLMP co-localizes with tight junction proteins, and is therefore claimed as a tight junction-associated protein. Because tight junction proteins play an important role in proliferation, we have suggested that loss-of-function of CLMP might affect proliferation. Moreover, it was shown that transfection of human CLMP into MDCK cells increases transepithelial resistance. Whether it is proliferation, or transepithelial resistance, or indeed another process in which CLMP plays a crucial role and that has impact on the pathophysiology of CSBS, is still unknown. As previously reported, transient transfection of human CLMP into T84 cells showed localization of WT-CLMP at the cell membrane and mislocalization of mutant-CLMP in the cytoplasm. Although others have shown that transfection of human CLMP into MDCK cells increases transepithelial electrical resistance, we did not observe any differences in the transepithelial electrical resistance in T84 cells. We cannot say whether this discrepancy is due to the use of distinct cell types or to the fact that CLMP is simply not involved in this process. MDCK cells are kidney cells derived from a seemingly normal adult female cocker spaniel. Many different strains of the MDCK cell line are available and the transepithelial resistance in these different strains differs depending on the tight junction proteins that are expressed. This illustrates that even in the same cell line, different results can be obtained.