Modulation de l'invasion tumorale par l'altération de l'identité cellulaire dans les gliomes pédiatriques infiltrants de la ligne médiane

Le résumé fourni par la source

Diffuse midline gliomas (DMG) are incurable tumors originating from midline structures that infiltrate throughout the brain. Evidence suggests that oligodendrocyte progenitor cells (OPC), a highly migratory cell population during brain development, serve as the cell-of-origin for DMG. However, to date, there has been no direct study investigating the link between the cell identity of DMG cells and their invasive behavior. My PhD work is the first to validate the positive correlation between expression of NKX2-2, a master transcription factor, and the invasiveness of DMG cells. Knocking down NKX2-2 using an shRNA approach resulted in the transition from OPC-like to neuroblast identity in highly invasive DMG cells, with a less invasive and less proliferative profile.It suggests that NKX2-2 modulates invasion via CDH11 and through RHO GTPases signaling pathways and the noncanonical WNT pathway. Moreover, the invasion process regulated by NKX2- 2 may also involve neuron-glioma synaptic interaction and the interconnection between glioma cells. Taken together, NKX2-2 and its downstream genes could represent interesting targets for reducing DMG invasion and improving survival rates in patients.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.