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<p>Mechanosensitive ion channel PIEZO2 translates microenvironmental forces into Ca²⁺-dependent signals that shape tumor behavior. Across cancers, PIEZO2 exhibits context-dependent roles, with evidence for both pro- and anti-tumor functions, depending on tissue type, molecular subtype, disease stage, and stromal context. This review synthesizes emerging insights into the multifaceted roles of PIEZO2 in cancer biology, summarize clinical correlations, highlight areas with concordant directionality (e.g., colorectal cancer, medulloblastoma) versus paradoxical findings (e.g., breast cancer across subtypes, gastric cancer by differentiation status), and provide a pragmatic framework for precision, context aware targeting. While PIEZO2 remains attractive for combination strategies (anti-angiogenesis, barrier modulation, dormancy escape, radio/chemo sensitization) and cancer pain interfaces, the field lacks truly PIEZO2 selective small molecule modulators. We propose feasible future priorities encompassing both pharmacologic and non-pharmacologic strategies to accelerate translational applications.</p><p><b>Graphical Abstract</b></p><p></p>

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PIEZO2 in tumors: from mechanobiological switches to activity-targeted therapies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月1日

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  • Dan-xia Huang,
  • Qiu-zhi Zhou,
  • Hong-mei Luo,
  • Mohammad Nasb,
  • Yi-zhou Liu,
  • Yu-jie Yang,
  • Hong Chen

摘要

Mechanosensitive ion channel PIEZO2 translates microenvironmental forces into Ca²⁺-dependent signals that shape tumor behavior. Across cancers, PIEZO2 exhibits context-dependent roles, with evidence for both pro- and anti-tumor functions, depending on tissue type, molecular subtype, disease stage, and stromal context. This review synthesizes emerging insights into the multifaceted roles of PIEZO2 in cancer biology, summarize clinical correlations, highlight areas with concordant directionality (e.g., colorectal cancer, medulloblastoma) versus paradoxical findings (e.g., breast cancer across subtypes, gastric cancer by differentiation status), and provide a pragmatic framework for precision, context aware targeting. While PIEZO2 remains attractive for combination strategies (anti-angiogenesis, barrier modulation, dormancy escape, radio/chemo sensitization) and cancer pain interfaces, the field lacks truly PIEZO2 selective small molecule modulators. We propose feasible future priorities encompassing both pharmacologic and non-pharmacologic strategies to accelerate translational applications.

Graphical Abstract