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Intermediate filaments promote glioblastoma cell invasion by controlling cell deformability and mechanosensitive gene expression
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Posted 28 Jun, 2023 on Research Square.. Cancer invasion turns a locally growing tumour into a live-threatening disease. Unravelling the molecular signature of invasive cells and their mechanisms of invasion is essential to identify therapeutic targets. While the cytoskeleton is known to support cell mechanical properties required for invasion, the role of intermediate filaments (IFs) is often overlooked. Here we investigated the role of IFs in glioblastoma (GBM), the most common and aggressive primary brain tumour, which is characterized by its high invasive capacity, allowing it to evade classical treatments. Following in silico analysis of published single cell RNA sequencing data of GBM samples which shows that high expression of IF genes correlates with pro-migration markers, we generated IF-depleted GBM cells to demonstrate that the cytoplasmic IF network promotes GBM cell invasion in vitro and in vivo. Mechanical measurement and biochemical analyses show that IFs influence cell invasion by increasing cell stiffness, limiting nuclear deformations, and controlling mechanosensitive gene expression and matrix degradation. Our results reveal the crucial role of IFs in tumour cell mechanics and invasion and suggest that the IF expression pattern can serve as a molecular marker of cells driving glioblastoma invasion.
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