In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.

The TGF family member NODAL, primarily known for its role during embryonic development, has also been associated with tumor progression in a number of cancers. Some of the evidence supporting its involvement in melanoma has appeared contradictory, suggesting that NODAL in this context might rely on a non-canonical mode of signaling. To investigate this possibility we studied how a deletion of NODAL affected cell behavior in a metastatic melanoma cell line. The mutation does prevent melanoma cells from acquiring an invasive behavior. However, this phenotype was found to result not from the absence of NODAL, but from the disabled expression of a natural antisense transcript of NODAL now called LADON. Its expression promotes the mesenchymal to amoeboid transition that is critical to melanoma cells' invasiveness. Our analyses revealed that the increase in LADON expression necessary to complete this transition is dependent on WNT/ -CATENIN signaling and that its downstream effectors include MYCN and the metastasis suppressor NDRG1, which controls changes in the cytoskeleton. These results identify LADON as a player in the network of interactions governing tumor progression in melanoma, and suggest a similar implication in other cancer types.