{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:24:23Z","timestamp":1791923063070,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020SF\u2010123"],"award-info":[{"award-number":["2020SF\u2010123"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020SF\u2010195"],"award-info":[{"award-number":["2020SF\u2010195"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901838"],"award-info":[{"award-number":["81901838"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Emerging evidence implicates mechanotransduction pathways in modulating bladder carcinoma (BLCA) pathogenesis. However, the crosstalk between Piezo1 and integrin \u03b21 (ITGB1) in extracellular matrix (ECM) stiffness\u2010driven tumorigenesis remains a critical knowledge gap. This study systematically investigates the functional synergy of Piezo1\/ITGB1 in orchestrating ECM biomechanical remodeling to fuel BLCA progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Utilizing an integrative framework combining clinical histopathology, in\u00a0vivo tumor models, multiomics profiling, molecular biology experiments, matrix stiffness quantification, calcium flux analysis, and YAP signaling interrogation, we dissected the mechanochemical interplay between Piezo1\/ITGB1 activation and ECM dynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical and animal data revealed that Piezo1\/ITGB1 coactivation was strongly correlated with ECM stiffness\u2010induced BLCA proliferation and poor clinical prognosis. The coordinated expression of Piezo1\/ITGB1 enhanced ECM interaction, organization, adhesion, and collagen binding. Crucially, Piezo1\/ITGB1 overexpression promoted cancer development by suppressing apoptosis and enhancing proliferation. Mechanistically, ECM stiffness triggered Piezo1\/ITGB1\u2010dependent Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, which facilitated YAP nuclear translocation and subsequent upregulation of downstream targets CTGF, \u03b1\u2010SMA, and COL1A1, thereby reinforcing collagen deposition and matrix stiffening.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our work uncovers a feedforward mechano\u2010oncogenic axis wherein Piezo1\/ITGB1 cooperativity converts ECM cues into sustained protumorigenic signaling through Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/YAP\u2010mediated transcriptional reprogramming. This paradigm redefines ECM stiffness not merely as a pathological consequence but as an active driver of BLCA progression, proposing precision targeting of the Piezo1\/ITGB1 triad as a mechanotherapy strategy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71059","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T02:10:27Z","timestamp":1752718227000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Piezo1\/\n                    <scp>ITGB1<\/scp>\n                    Synergizes With Ca\n                    <sup>2+<\/sup>\n                    \/\n                    <scp>YAP<\/scp>\n                    Signaling to Propel Bladder Carcinoma Progression via a Stiffness\u2010Dependent Positive Feedback Loop"],"prefix":"10.1002","volume":"14","author":[{"given":"Minghai","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Basic Medical Sciences, Xi'an Medical University  Xi'an China"},{"name":"Department of Urology The First Affiliated Hospital, Xi'an Jiaotong University  Xi'an China"},{"name":"Department of Thoracic Surgery Tangdu Hospital, Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-7802","authenticated-orcid":false,"given":"Jianpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital, Xi'an Jiaotong University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Tangdu Hospital, Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxuan","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Urology The 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