# Piezo-type mechanosensitive ion channel component 1: a mechano-bioenergetic transducer in the tumour microenvironment

## TL;DR

Piezo1 is a key ion channel in the tumor microenvironment that links mechanical signals to cancer progression and immune evasion.

## Contribution

This review systematically elucidates Piezo1's role in the tumor microenvironment and its potential as a therapeutic target.

## Key findings

- Piezo1 activation in endothelial and immune cells promotes tumor angiogenesis and immune evasion.
- Cell type-specific Piezo1 regulation creates a 'mechano-immuno' network that drives tumor progression.
- Targeting Piezo1 offers a promising but challenging strategy requiring precise signaling modulation.

## Abstract

As a pivotal mechanosensitive ion channel, Piezo-type mechanosensitive ion channel component 1 (Piezo1) converts mechanical stimuli into biochemical signals that regulate key oncogenic processes, including tumour cell proliferation, migration and invasion. Emerging evidence demonstrates that Piezo1 is widely expressed across various cellular compartments of the tumour microenvironment (TME), and its elevated expression strongly correlates with adverse clinical outcomes. A comprehensive understanding of the complex interactions between Piezo1 activation and cytokine networks in different TME cell populations is therefore essential for developing innovative and effective anti-tumour therapeutic strategies. In this review, we aimed to highlight the molecular mechanisms of Piezo1, systematically elucidating how the mechanical stimulation-Piezo1 signalling pathway within the TME contributes to tumour immune escape and malignant progression. Furthermore, we summarized current research advances in Piezo1-targeting drugs and clinical trials, and discuss strategies to improve tissue specificity while minimizing off-target effects.

A comprehensive literature review was conducted, focusing on the specific mechanisms through which Piezo1 regulates endothelial cells, immune cells, cancer-associated fibroblasts and the extracellular matrix within the TME. Activation of Piezo1 in endothelial and immune cells promotes tumour angiogenesis and immune evasion.

Piezo1 plays a critical role in tumour progression and represents a promising therapeutic target for cancer treatment

Piezo1 serves as a central mechanosensitive ion channel that integrates physical and biochemical cues within the tumour microenvironment, driving angiogenesis, immune evasion and extracellular matrix remodelling.Cell type-specific regulation of Piezo1 in endothelial cells, immune cells and cancer-associated fibroblasts establishes a complex ‘mechano-immuno’ network that critically shapes tumour progression.Targeting Piezo1 and its downstream mechanotransduction pathways represents a promising yet challenging therapeutic strategy, requiring precise modulation of its signalling specificity and tissue selectivity.

Piezo1 serves as a central mechanosensitive ion channel that integrates physical and biochemical cues within the tumour microenvironment, driving angiogenesis, immune evasion and extracellular matrix remodelling.

Cell type-specific regulation of Piezo1 in endothelial cells, immune cells and cancer-associated fibroblasts establishes a complex ‘mechano-immuno’ network that critically shapes tumour progression.

Targeting Piezo1 and its downstream mechanotransduction pathways represents a promising yet challenging therapeutic strategy, requiring precise modulation of its signalling specificity and tissue selectivity.