Polycystin-1 and hydrostatic pressure are implicated in glioblastoma pathogenesis in vitro.

Abstract

The mechanobiological aspects of glioblastoma (GBM) pathogenesis are largely unknown. Polycystin‐1 (PC1) is a key mechanosensitive protein which perceives extracellular mechanical cues and transforms them into intracellular biochemical signals that elicit a change in cell behaviour. The aim of the present study was to investigate if and how PC1 participates in GBM pathogenesis under a mechanically induced microenvironment. Therefore, we subjected T98G GBM cells to continuous hydrostatic pressure (HP) and/or PC1 blockade and evaluated their effect on cell behaviour, the activity of signalling pathways and the expression of mechano‐induced transcriptional regulators and markers associated with properties of cancer cells. According to our data, PC1 and HP affect GBM cell proliferation, clonogenicity and migration; the diameter of GBM spheroids; the phosphorylation of mechanistic target of rapamycin (mTOR), extracellular signal‐regulated kinase (ERK) and focal adhesion kinase (FAK); the protein expression of transcription cofactors YES‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ); and the mRNA expression of markers related to anti‐apoptosis, apoptosis, angiogenesis, epithelial to mesenchymal transition (EMT) and proliferation. Together, our in vitro results suggest that PC1 plays an important role in GBM mechanobiology.