PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β-catenin axis

Sep 22, 2026

Background: PIEZO1 shows context-dependent roles across cancers and developmental stages. Objective: explore PIEZO1 function and underlying mechanism in lung adenocarcinoma (LUAD) cells. Methods: LUAD cell lines were treated with the PIEZO1 inhibitor GsMTx4 and agonist Yoda1; PIEZO1 expression was assessed by RT-qPCR and western blotting. Functional assays measured proliferation, invasion, migration, EMT marker proteins, and apoptosis. ROS agonists/inhibitors and Wnt/β-catenin pathway inhibitors were used to probe mechanistic links. Results: GsMTx4 increased proliferation, invasion, migration, EMT-related protein expression, and reduced apoptosis, whereas Yoda1 reversed these effects. GsMTx4 reduced ROS production and mitigated BAY 87–2243-induced ROS, apoptosis, and proapoptotic markers; iCRT3 counteracted GsMTx4-induced EMT and enhanced apoptosis. Conclusion: PIEZO1 suppresses cancer by regulating the ROS/Wnt/β-catenin axis.

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Abstract

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DOI: 10.1111/1759-7714.15278 ORIGINA L ARTICLE PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β-catenin axis Haimei Bo 1,2 | Qi Wu 1 | Chaonan Zhu 2,3 | Yang Zheng 3 | Guang Cheng 2 | Lihua Cui 2 1Tianjin Medical University General Hospital, Tianjin, China 2North China University of Science and Technology, Tangshan, China 3Graduate School, Tianjin Medical University, Tianjin, China Correspondence Qi Wu, Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. [Email:](Email: wq572004@163.com)[ wq572004@163.com](Email: wq572004@163.com) Funding information Science Research Project of Hebei Education Department, Grant/Award Number: QN2019174 Abstract Background: PIEZO1 works differently in different cancers and at different stages of development. The objective of the current study was to explore the function and underlying mechanism of PIEZO1 in lung adenocarcinoma (LUAD) cells. Methods: Different LUAD cell lines were treated with PIEZO1 inhibitor (GsMTx4) and agonist (Yoda1), and the expression of PIEZO1 in LUAD cells was detected using real-time quantitative PCR (RT-qPCR) and western blotting. The effects of PIEZO1 on invasion, migration and epithelial-mesenchymal transition (EMT) markers protein expression of LUAD cells were detected using the MTT assay, flow cytometry, transwell assay, wound-healing assay, and western blotting. Reactive oxygen species (ROS) agonists (BAY 87–2243) and inhibitors (NAC) and Wnt/β -catenin pathway inhibitors (iCRT3) were selected to treat A549 cells to investigate the mechanism of PIEZO1 on ROS production and Wnt/β-catenin expression in A549 cells. Results: In A549, NCI-H1395, and NCI-H1975 cells, GsMTx4 promoted cell proliferation, invasion, migration, upregulated EMT-related marker protein expression, and inhibited cell apoptosis, while Yoda1 exerted effects opposite to those of GsMTx4 . In A549 cells, GsMTx4 can reduce ROS production, it also inhibited ROS production, apoptosis, and downregulated proapoptotic markers induced by BAY 87–2243. Importantly, BAY 87–2243 blocked the effect of GSMTX4-induced Wnt/β-catenin overexpression. Similarly, Yoda1 can reduce the effect of NAC. In addition, iCRT3 can block the upregulation of EMT-related marker proteins by GsMTx4, and increase apoptosis and decrease cell invasion and migration. Conclusion: In summary, PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β-catenin axis, providing a new perspective on the role of mechanosensitive channel proteins in cancer. KEYW ORD S EMT, lung adenocarcinoma, PIEZO1, ROS, Wnt/β-catenin INTRODUCTION Regarded as one of the most common malignancies, lung cancer is the leading cause of cancer-related deaths globally.1 Lung adenocarcinoma (LUAD) is the most common type of lung cancer.2 Despite the emergence and development of new therapies in recent years, LUAD remains an aggressive and rapidly lethal cancer type.3 In 2022, lung cancer was among the top three most common cancers in males and females.4 Therefore, exploring the molecular mechanisms underlying LUAD progression is crucial to identify new therapeutic targets. Epithelial-to-mesenchymal transition (EMT) is a major driver of cancer progression.5 Recent studies have shown This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd. that EMT promotes the invasive and metastatic abilities of lung cancer.6,7 PIEZO proteins are ion channels that mediate cellular mechanosensory transduction, including PIEZO1 and PIEZO2 .8 PIEZO protein is a novel mechanosensitive cation channel protein discovered in a mouse neuroblastoma cell line in 2010 .9 As a member of the PIEZO family, P

FAQs

What is the main objective of the study on PIEZO1 in LUAD cells?

To explore PIEZO1’s function and underlying mechanism in lung adenocarcinoma (LUAD) cells, focusing on how it affects proliferation, apoptosis, ROS production, and the Wnt/β-catenin pathway.

How were PIEZO1 effects tested in LUAD cell lines?

LUAD cells were treated with the PIEZO1 inhibitor GsMTx4 and agonist Yoda1, with PIEZO1 expression measured by RT-qPCR and western blotting. Proliferation, invasion, migration, EMT markers, and apoptosis were assessed using assays including MTT, flow cytometry, transwell, wound-healing, and western blotting.

What does the study report about ROS and Wnt/β-catenin signaling?

GsMTx4 reduced ROS production and suppressed ROS- and BAY 87–2243-induced apoptosis and proapoptotic markers. BAY 87–2243 blocked GsMTx4-induced Wnt/β-catenin overexpression, and iCRT3 blocked the upregulation of EMT marker proteins by GsMTx4 while increasing apoptosis and reducing invasion and migration.

Sep 22, 2026

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