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This is driven by a prominent cell type in the TME, cancer\u2010associated fibroblasts (CAFs), which increases tissue stiffness via extracellular matrix deposition and remodeling. Currently, it is unclear whether there are also physical changes to CAFs at the cellular level and, if so, how they relate to patient outcome. Here, it is shown that CAFs have distinct morphological and biomechanical features from normal fibroblasts. Matched, patient\u2010derived CAFs and non\u2010malignant prostate fibroblasts (NPFs) from 35 patients with primary prostate cancer are examined. Morphologically, CAFs have more aligned stress fibers and larger and more elongated nuclei, based on quantitative image analysis of confocal microscopy images. In addition, single\u2010cell mechanical measurements using real\u2010time deformability cytometry showed that CAFs are larger and stiffer than NPFs. These changes are consistent across patients and validated with atomic force microscopy. A combined morphomechanical score encompassing these features is significantly associated with patient outcome. In transcriptomic analyses, the score is correlated with microtubule dynamics and a myofibroblast phenotype. Importantly, it is also demonstrated that morphomechanical features of prostate fibroblasts are modified by approved treatments for prostate cancer, such as docetaxel, and other small molecular inhibitors, particularly those targeting FGFR. In summary, changes in cellular morphomechanical properties are a consistent feature of CAFs and are associated with patient outcome. Moreover, cellular morphomechanical properties can be therapeutically targeted, potentially providing a new strategy for manipulating the TME to control cancer progression.<\/jats:p>","DOI":"10.1002\/advs.202522440","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:50:07Z","timestamp":1767873007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell Morphomechanics of Prostate Cancer\u2010Associated Fibroblasts Identifies Distinct Features Associated with Patient Outcome"],"prefix":"10.1002","volume":"13","author":[{"given":"Antje","family":"Garside","sequence":"first","affiliation":[{"name":"Center for Molecular and Cellular Bioengineering (CMCB) BIOTEC Dresden University of Technology (TUD)  01307 Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Jacobi","sequence":"additional","affiliation":[{"name":"Center for 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Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birunthi","family":"Niranjan","sequence":"additional","affiliation":[{"name":"Melbourne Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Teng","sequence":"additional","affiliation":[{"name":"Melbourne Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Choo","sequence":"additional","affiliation":[{"name":"Melbourne Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes Low Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Bioengineering (CMCB) BIOTEC Dresden University of Technology (TUD)  01307 Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail P","family":"Risbridger","sequence":"additional","affiliation":[{"name":"Melbourne Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"},{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria 3000 Australia"},{"name":"Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria 3010 Australia"},{"name":"Cabrini Institute Cabrini Health  Malvern Victoria 3144 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell G","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Melbourne Urological Research Alliance Biomedicine Discovery Institute Monash University  Clayton Victoria 3800 Australia"},{"name":"Peter MacCallum Cancer Centre  Melbourne Victoria 3000 Australia"},{"name":"Sir Peter MacCallum Department of Oncology The University of Melbourne  Melbourne Victoria 3010 Australia"},{"name":"Cabrini Institute Cabrini Health  Malvern Victoria 3144 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-0394","authenticated-orcid":false,"given":"Anna V.","family":"Taubenberger","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Bioengineering (CMCB) BIOTEC Dresden University of Technology (TUD)  01307 Dresden Germany"},{"name":"Leibniz\u2010Institute of Polymer Research Dresden (IPF) Max Bergmann Center of Biomaterials  01069 Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_8_2_1","unstructured":"European Association of Urology Guidelines on Prostate Cancer European Association of Urology2023."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0751"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00613-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.05.026"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908785699351"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13010067"},{"key":"e_1_2_8_9_1","first-page":"599","volume":"17","author":"Kunz\u2010Schughart L. 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