31.    Evaluating Pin1 as a therapeutic target for invasive tumors of CNS: Neuroblastoma             and Glioblastoma cell models

Cancer is the second leading cause of death globally, with more than eight million deaths reported in 2015 by the World Health Organization. The development of novel therapies against cancer is a worldwide health priority due to the high incidence of this disease and the lack of effective therapies. Conventional cancer therapies have a very limited ability to distinguish tumour cells from normal cells. Neuroblastoma (NBL) and Glioblastoma (GBL) are invasive tumors of the CNS, NBL is mainly a childhood cancer that develops from tissues that form the sympathetic nervous system, however, GBL can occur at any age but tends to occur more often in older adults. The ability to interfere exclusively with mechanisms responsible for tumorigenesis can provide the basis for the generation of new therapeutic strategies. Pin1 is an isomerase frequently overexpressed in various tumours and has become an attractive molecule in cancer research. Our results showed that overexpression of Pin1 in cellular models of NBL and GBL did not significantly impact cell growth in normal cell culture conditions. However, NBL cells stably overexpressing Pin1 showed a significant anchorage-independent growth when cultured in soft-agar, but this was not the case for GBL cells. Notably, this kind of proliferation, which is considered a hallmark of carcinogenesis, is completely reversed in NBL cells in presence of Juglone, a Pin1 inhibitor. Also, wound healing
assay revealed that Juglone reduced the migration ability of NBL cells, again, we did not find difference in cell migration in GBL cells overexpressing Pin1. We concluded that inhibition of Pin1 altered tumor-associated phenotypes of NBL cells but not of GBL cells, evidencing that these two types of cancer present different mechanisms for tumorigenesis. More studies are being carried out to validate Pin1 as a possible target of new therapies against NBL.