Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Biopathology, 'Aeginition' Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
J Cell Mol Med. 2022 Mar;26(5):1699-1709. doi: 10.1111/jcmm.17212. Epub 2022 Feb 1.
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.
神经胶母细胞瘤（GBM）发病机制的力学生物学方面在很大程度上尚未可知。多囊蛋白-1（PC1）是一种关键的机械敏感蛋白，它感知细胞外的机械线索，并将其转化为细胞内的生化信号，从而引发细胞行为的改变。本研究的目的是探讨 PC1 是否以及如何在机械诱导的微环境下参与 GBM 的发病机制。因此，我们使 T98G GBM 细胞持续承受静水压力（HP）和/或 PC1 阻断，并评估其对细胞行为、信号通路活性以及机械诱导转录调节剂和与癌细胞特性相关标志物的表达的影响。根据我们的数据，PC1 和 HP 影响 GBM 细胞的增殖、集落形成能力和迁移；GBM 球体的直径；雷帕霉素（mTOR）、细胞外信号调节激酶（ERK）和粘着斑激酶（FAK）的磷酸化；转录共激活因子 YES 相关蛋白（YAP）和含 PDZ 结合基序的转录共激活因子（TAZ）的蛋白表达；以及与抗凋亡、凋亡、血管生成、上皮间质转化（EMT）和增殖相关的标志物的 mRNA 表达。总之，我们的体外结果表明，PC1 在 GBM 的力学生物学中发挥着重要作用。
