Impact of phospholipase C β1 in glioblastoma: a study on the main mechanisms of tumor aggressiveness
Stefano Ratti, Maria Vittoria Marvi, Sara Mongiorgi, Eric Owusu Obeng, Isabella Rusciano, Giulia Ramazzotti, Luca Morandi, Sofia Asioli, Matteo Zoli, Diego Mazzatenta, Pann‐Ghill Suh, Lucia Manzoli, Lucio Cocco
Abstract
Glioblastoma represents the most lethal brain tumor in adults. Several studies have shown the key role of phospholipase C β1 (PLCβ1) in the regulation of many mechanisms within the central nervous system suggesting PLCβ1 as a novel signature gene in the molecular classification of high-grade gliomas. This study aims to determine the pathological impact of PLCβ1 in glioblastoma, confirming that PLCβ1 gene expression correlates with glioma's grade, and it is lower in 50 glioblastoma samples compared to 20 healthy individuals. PLCβ1 silencing in cell lines and primary astrocytes, leads to increased cell migration and invasion, with the increment of mesenchymal transcription factors and markers, as Slug and N-Cadherin and metalloproteinases. Cell proliferation, through increased Ki-67 expression, and the main survival pathways, as β-catenin, ERK1/2 and Stat3 pathways, are also affected by PLCβ1 silencing. These data suggest a potential role of PLCβ1 in maintaining a normal or less aggressive glioma phenotype.