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To model these forces, we generated \u201cmechanoresistant\u201d (MR) LNCaP and PC3 prostate cancer (PCa) cell lines by repeatedly exposing cells to high\u2011intensity (HI) FSS (3950 dyn\/cm\n                    <jats:sup>2<\/jats:sup>\n                    ). LNCaP MR cells acquired marked resistance to HI FSS, exhibiting significantly reduced apoptosis, while PC3 cells demonstrated innate resistance. Bulk RNA\u2011sequencing revealed that LNCaP and PC3 MR cells developed distinct molecular programs.\n                    <jats:italic>CALB2<\/jats:italic>\n                    (calretinin) emerged as a mechanoresistance gene selectively upregulated in PC3 MR cells, and\n                    <jats:italic>CALB2<\/jats:italic>\n                    knockout significantly reduced viability upon re\u2011exposure to HI FSS. Analysis of\n                    <jats:italic>CALB2<\/jats:italic>\n                    \u2011high PCa cases captured patient\u2011level molecular heterogeneity, suggesting a mechanoadaptive state rather than a uniform aggressiveness\u2010driven tumor phenotype. This was consistent with the absence of correlation between\n                    <jats:italic>CALB2<\/jats:italic>\n                    levels and Gleason Scores. In an orthotopic PCa mouse model, the PC3 MR condition displayed the most aggressive early tumor growth and the largest endpoint tumor volumes, consistent with enhanced proliferation. Together, these findings demonstrate that PCa cells acquire discrete mechanoadaptive phenotypes under extreme FSS, revealing targetable pathways to limit metastatic competence.\n                  <\/jats:p>","DOI":"10.1002\/advs.76535","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:23:14Z","timestamp":1784550194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>CALB2<\/i>\n                    is a Mechanoresistance Gene in Metastatic Prostate Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Abigail R.","family":"Fabiano","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"},{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen C.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Taufalele","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna A.","family":"Dombroski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Aalaei","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Schyler J.","family":"Rowland","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa S.","family":"Cant\u00fa","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria T.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha V.","family":"Knoblauch","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Reinhart\u2010King","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4643-3663","authenticated-orcid":false,"given":"Michael R.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Rice University  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010022\u201002136\u20103"},{"key":"e_1_2_10_3_1","unstructured":"A. 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