Pro-tumoral Ca2+ signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma.

Ion channel-mediated cytosolic Ca2+ oscillations play a crucial role in promoting glioblastoma growth. Here, we have studied the expression and functional roles of prospective oncogenic targets Slowpoke and Ca-α1T channels in a Drosophila melanogaster glioma model. While their mammalian orthologs have shown to be relevant for glioblastoma cell viability in vitro, there is no data available about their oncogenic function in a complex in vivo environment. Using RNAis against Slowpoke and Ca-α1T specifically expressed in glial cells, we show that both channels contribute to magnify Ca2+ activity and ensuing Ca2+-dependent pro-tumoral pathways, glial cell proliferation and membrane extension. However, only the knockdown of Slowpoke extends the lifespan of glioma-bearing individuals and reverses glioma-induced neurodegeneration, suggesting its functional association with other Ca2+ channels in addition to Ca-α1T. Furthermore, RNAseq transcriptomic analysis reveals that Slowpoke regulates excitatory neurotransmission, highlighting its potential as a therapeutic target in glioblastoma.