Abstract
Cell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is one of the most aggressive and frequent primary brain tumors. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here, we describe in a Drosophila model how glioblastoma cells produce ImpL2, an antagonist of the insulin pathway, which targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue synapse loss and to delay the premature death caused by glioma. Therefore, signals from glioblastoma to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.
Highlights
Cancer is one of the leading causes of mortality worldwide and is expected to be responsible for 15 million deaths in 2020 (65% in less developed countries) according to the World Health Organization
We previously reported a reduction in the number of synapses in the neuromuscular junction (NMJ) of adult flies caused by GB progression (Portela et al, 2019b)
We established that tumoral progression depended on the formation of a network of protrusions named tumor microtubules (TMs), to human GB (Osswald et al, 2015; Portela et al, 2019b)
Summary
Cancer is one of the leading causes of mortality worldwide and is expected to be responsible for 15 million deaths in 2020 (65% in less developed countries) according to the World Health Organization. GB stands out because it is the most frequent and a very aggressive primary brain tumor It is originated from glial cells and causes death within the first year after diagnosis (Bi & Beroukhim, 2014), despite standard treatments such as resection, radiotherapy, and chemotherapy. This is accompanied by broad neurological dysfunctions (Messaoudi et al, 2015). Brain tumors cause cognitive decline and neuronal dysfunction (reviewed in Gehrke et al [2013] and Bergo et al [2016]) These cognitive defects are consistent with typical neurodegenerative-associated symptoms such as synapse loss and mitochondrial alterations (Granholm et al, 2010; Levenson et al, 2014)
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