Журнал болезни Альцгеймера и паркинсонизма

Абстрактный

Neural Cancer Stem Cells: Focusing on Chromosome Ends

Fernando Pires Hartwig*

Telomeres are DNA tandem repeats associated with six proteins located at chromosome ends. Telomere shortening happens after each replication round in the majority of human cells, including adult stem cells, leading to telomere dysfunction and activation of senescence and/or apoptosis. In this commentary, key studies evidencing that telomerase overexpression (which is the most common telomere lengthening mechanism in cancer) confer stem-like properties to neural cells with tumorigenic potential, which is in accordance to previously proposed models of TERT overexpression as a mechanism for the emergence of neural cancer stem cells. In addition, the recent finding that telomerase inhibition is a promising anti-neural cancer stem cell therapy (at least in gliomas) is confronted with other studies, resulting in the identification of potential limitations: the presence of alternative lengthening of telomeres in neural cancer stem cells (already identified in glioma stem cells) and of the possibility that short telomeres is not an universal feature of neural cancer stem cells. Further investigation regarding telomere length measurement in neural cancer stem cells of different origins and development of clinically feasible and applicable methods to distinguish telomerase-positive from ALT-positive neural cancer stem cells are pointed as important perspectives to better understand the potential of the promising telomerase inhibition-based therapy to fight neural cancer stem cells.