Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets

Author:

Di XingpengORCID,Gao Xiaoshuai,Peng Liao,Ai Jianzhong,Jin Xi,Qi ShiqianORCID,Li Hong,Wang KunjieORCID,Luo Deyi

Abstract

AbstractCellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.

Funder

National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University

National Natural Science Foundation of China

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics

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