{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:32:02Z","timestamp":1792081922909,"version":"4.4.0"},"reference-count":68,"publisher":"Wiley","issue":"41","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073194"],"award-info":[{"award-number":["82073194"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extracellular matrix (ECM) stiffness\u2010mediated mechanotransduction is a common signaling scheme in both physiological and pathological contexts; however, its molecular mechanisms remain incompletely understood. Polycystin\u20101 is a transmembrane protein that is known to participate in mechano\u2010transduction. Here, it is demonstrated that, in response to extracellular collagen and increased ECM stiffness, polycystin\u20101 interacts with disheveled\u2010associated activator of morphogenesis 1 (Daam1), a cytoskeletal regulator, thereby promoting microfilament remodeling, cellular protrusion formation, and enhanced motility of tumor cells through activating the RhoA signaling axis. Wild\u2010type polycystin\u20101 is susceptible to proteolytic cleavage at the G protein\u2010coupled receptor proteolysis site. Using atomic force microscopy\u2010based single\u2010molecule force spectroscopy, direct evidence is provided that polycystin\u20101 variants R3039H and L3048H exhibit reduced cleavage susceptibility in vitro. Notably, R3039H is associated with lymphatic and distant metastasis in breast cancer and augments mechanotransduction by facilitating the nuclear translocation of Yes\u2010associated protein and upregulating the expression of connective tissue growth factor and collagen in tumor cells and cancer\u2010associated fibroblasts, respectively. Collectively, our findings identify polycystin\u20101 as a mechanosensor of collagen and ECM stiffness that modulates tumor cell migration via the Daam1\/RhoA\/YAP signaling cascade.<\/jats:p>","DOI":"10.1002\/advs.202509846","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T19:42:52Z","timestamp":1754941372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polycystin\u20101 Mutant Alters Mechanotransduction in Response to Collagen and Extracellular Matrix Stiffness via Daam1\u2010Dependent Microfilament Remodeling"],"prefix":"10.1002","volume":"12","author":[{"given":"Jiaofeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Nanjing Medical University  Nanjing Jiangsu 211166 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