Cell-to-cell communication mediates glioblastoma progression in Drosophila.pdf (7.76 MB)
Cell-to-cell communication mediates glioblastoma progression in drosophila
journal contribution
posted on 2021-01-18, 02:14 authored by Marta Portela-EstebanMarta Portela-Esteban, T Mitchell, S Casas-Tintó© 2020. Published by The Company of Biologists Ltd. Glioblastoma (GB) is the most aggressive and lethal tumour of the central nervous system (CNS). GB cells grow rapidly and display a network of projections, ultra-long tumour microtubes (TMs), that mediate cell to cell communication. GB-TMs infiltrate throughout the brain, enwrap neurons and facilitate the depletion of the signalling molecule wingless (Wg)/WNT from the neighbouring healthy neurons. GB cells establish a positive feedback loop including Wg signalling upregulation that activates cJun N-terminal kinase (JNK) pathway and matrix metalloproteases (MMPs) production, which in turn promote further TMs infiltration, GB progression and neurodegeneration. Thus, cellular and molecular signals other than primary mutations emerge as central players of GB. Using a Drosophila model of GB, we describe the temporal organisation of the main cellular events that occur in GB, including cell-to-cell interactions, neurodegeneration and TM expansion. We define the progressive activation of JNK pathway signalling in GB mediated by the receptor Grindelwald (Grnd) and activated by the ligand Eiger (Egr)/TNFα produced by surrounding healthy brain tissue. We propose that cellular interactions of GB with the healthy brain tissue precede TM expansion and conclude that non-autonomous signals facilitate GB progression. These results contribute to deciphering the complexity and versatility of these incurable tumours.
Funding
We acknowledge the support of the Confocal Microscopy unit and Molecular Biology unit at the Cajal Institute for their help with this project. Research was funded by grant BFU2015-65685P from the Spanish Ministry of Science and Innovation (MICINN).
History
Publication Date
2020-09-29Journal
Biology OpenVolume
9Issue
9Article Number
ARTN bio053405Pagination
14p.Publisher
COMPANY BIOLOGISTS LTDISSN
2046-6390Rights Statement
The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.Publisher DOI
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Science & TechnologyLife Sciences & BiomedicineBiologyLife Sciences & Biomedicine - Other TopicsGliaCancerGlioblastomaTumour microtubesJNKNeurodegenerationWORLD-HEALTH-ORGANIZATIONJNK-DEPENDENT APOPTOSISCENTRAL-NERVOUS-SYSTEMMATRIX METALLOPROTEINASESMALIGNANT GLIOMAEPITHELIAL-CELLSMODEL SYSTEMEXPRESSIONMMP-9RECEPTOR
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