Mechanosensitive Ion Channel PIEZO1 Signaling in the Hall-Marks of Cancer: Structure and Functions

SIMPLE SUMMARY: Tumor cells obtain various unique characteristics, which known as hallmarks of cancers, including sustained proliferative signaling, apoptosis resistance, and metastasis. These characteristics are crucial for tumor cells survival and for supporting their rapid growth. Studies have revealed that tumorigenesis is also accompanied by alteration in mechanical properties. Tumor cells could sense various mechanical forces, such as compressive force, shear stress, and portal vein pressure, which in turn could affect tumor progression. Piezo1 is a mechanically sensitive ion channel protein that can be activated mechanically, and is closely related to various diseases. Recent studies showed that Piezo1 is overexpressed in numerous tumors and is associated with poor prognosis. Furthermore, previous studies revealed that Piezo1 mediates these cancer hallmarks, and thus links up mechanical forces with tumor progression. Therefore, the discovery of Piezo1 provides a new insight for elucidating the mechanism of tumor progression under a mechanical microenvironment. ABSTRACT: Tumor cells alter their characteristics and behaviors during tumorigenesis. These characteristics, known as hallmarks of cancer, are crucial for supporting their rapid growth, need for energy, and adaptation to tumor microenvironment. Tumorigenesis is also accompanied by alteration in mechanical properties. Cells in tumor tissue sense mechanical signals from the tumor microenvironment, which consequently drive the acquisition of hallmarks of cancer, including sustained proliferative signaling, evading growth suppressors, apoptosis resistance, sustained angiogenesis, metastasis, and immune evasion. Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a mechanically sensitive ion channel protein that can be activated mechanically and is closely related to various diseases. Recent studies showed that Piezo1 mediates tumor development through multiple mechanisms, and its overexpression is associated with poor prognosis. Therefore, the discovery of Piezo1, which links-up physical factors with biological properties, provides a new insight for elucidating the mechanism of tumor progression under a mechanical microenvironment, and suggests its potential application as a tumor marker and therapeutic target. In this review, we summarize current knowledge regarding the role of Piezo1 in regulating cancer hallmarks and the underlying molecular mechanisms. Furthermore, we discuss the potential of Piezo1 as an antitumor therapeutic target and the limitations that need to be overcome.