Portal de Periódicos da CAPES

A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression

2018; Cell Press; Volume: 100; Issue: 4 Linguagem: Inglês

10.1016/j.neuron.2018.09.046

1097-4199

Xin Chen, Siyi Wanggou, Ankur Bodalia, Min Zhu, Weifan Dong, Jerry J. Fan, Wen Yin, Hyun-Kee Min, Malini Hu, Diana Draghici, Wenkun Dou, Feng Li, Fiona J. Coutinho, Heather Whetstone, Michelle Kushida, Peter B. Dirks, Yuanquan Song, Chi‐chung Hui, Yu Sun, Lu‐Yang Wang, Xuejun Li, Xi Huang,

Caveolin-1 and cellular processes

Alteration of tissue mechanical properties is a physical hallmark of solid tumors including gliomas. How tumor cells sense and regulate tissue mechanics is largely unknown. Here, we show that mechanosensitive ion channel Piezo regulates mitosis and tissue stiffness of Drosophila gliomas, but not non-transformed brains. PIEZO1 is overexpressed in aggressive human gliomas and its expression inversely correlates with patient survival. Deleting PIEZO1 suppresses the growth of glioblastoma stem cells, inhibits tumor development, and prolongs mouse survival. Focal mechanical force activates prominent PIEZO1-dependent currents from glioma cell processes, but not soma. PIEZO1 localizes at focal adhesions to activate integrin-FAK signaling, regulate extracellular matrix, and reinforce tissue stiffening. In turn, a stiffer mechanical microenvironment elevates PIEZO1 expression to promote glioma aggression. Therefore, glioma cells are mechanosensory in a PIEZO1-dependent manner, and targeting PIEZO1 represents a strategy to break the reciprocal, disease-aggravating feedforward circuit between tumor cell mechanotransduction and the aberrant tissue mechanics. VIDEO ABSTRACT.