Mechanosensitive Ion Channels and Their Role in Cancer Cells

Abstract

Mechanical forces are an inherent element in the world around us. The effects of their action can be observed both on the macro and molecular levels. They can also play a prominent role in the tissues and cells of animals due to the presence of mechanosensitive ion channels (MIChs) such as the Piezo and TRP families. They are essential in many physiological processes in the human body. However, their role in pathology has also been observed. Recent discoveries have highlighted the relationship between these channels and the development of malignant tumors. Multiple studies have shown that MIChs mediate the proliferation, migration, and invasion of various cancer cells via various mechanisms. This could show MIChs as new potential biomarkers in cancer detection and prognosis and interesting therapeutic targets in modern oncology. Our paper is a review of the latest literature on the role of the Piezo1 and TRP families in the molecular mechanisms of carcinogenesis in different types of cancer.

Keywords: cancer; mechanoreceptors; mechanosensitive ion channels; piezo channels.

Figure 1

Mechanical stimuli, e.g., compression, membrane tension, poking, shear stress, stretching, or suction activates calcium influx through mechanosensitive ion channels. Then, calcium acts as a signal molecule on various pathways which may lead to, e.g., cell proliferation [43,44,45,46]. Two models of mechanosensitive ion channel gating have been established. (A) In the force-from-lipids model, alterations in lipid organization lead to channel activation; (B) In the force-from-filaments model, the causative factors are changes in the extracellular matrix and cytoskeleton [31,32,33,34,35,36,37,38].

Figure 2

Compression exerted on a breast cancer cell activates Piezo channels through which calcium flows in. Then, the ion induces activation of both Src and ERK pathways that cause the formation of invadopodia in the cell membrane. Invadopodia destroys the extracellular matrix and, thus, promotes cell migration [64,66].

Figure 3

Piezo1 downregulation is linked to higher expression of p53 and Bax. Furthermore, there is the upregulation of E-cadherin and a decrease in N-cadherin expression. As a result, the inhibition of migration and the invasion of tumor cells occurs slowing down the growth of tumors in vivo [98].

Figure 4

Piezo1 is involved in the activation of myeloid-derived suppressor cells (MDSCs): (1) Piezo1 overexpression, (2) HDAC hyperactivity, (3) MDSC recruitment, and (4) lower CD8+ T cell response in the tumor microenvironment [132,138].