{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:52:04Z","timestamp":1791377524744,"version":"4.3.2"},"reference-count":102,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"10","funder":[{"DOI":"10.13039\/100009727","name":"Hospital Research Foundation","doi-asserted-by":"publisher","award":["2019-038-83100"],"award-info":[{"award-number":["2019-038-83100"]}],"id":[{"id":"10.13039\/100009727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009727","name":"Hospital Research Foundation","doi-asserted-by":"publisher","award":["2023-CF-ABCRF-101-QA25343"],"award-info":[{"award-number":["2023-CF-ABCRF-101-QA25343"]}],"id":[{"id":"10.13039\/100009727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011713","name":"Worldwide Cancer Research","doi-asserted-by":"publisher","award":["22-0002"],"award-info":[{"award-number":["22-0002"]}],"id":[{"id":"10.13039\/100011713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE210100604"],"award-info":[{"award-number":["DE210100604"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT120100132"],"award-info":[{"award-number":["FT120100132"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1145319"],"award-info":[{"award-number":["GNT1145319"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1184809"],"award-info":[{"award-number":["GNT1184809"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000950","name":"Cancer Council South Australia","doi-asserted-by":"publisher","award":["GNT2019922"],"award-info":[{"award-number":["GNT2019922"]}],"id":[{"id":"10.13039\/501100000950","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Employment and Workplace Relations, Australian Government; Research Training Program"},{"name":"University of South Australia Postgraduate Award"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,3,6]]},"abstract":"<jats:p>Rapidly growing tumors experience high tissue-level forces, particularly when growing within a restricted space. These require counteracting by intracellular forces to prevent tissue damage. Here, we reveal the ion channel Piezo1 as a mechanosensor of compressive force, activating Rho\u2013Rho kinase (ROCK) mechanotransduction to generate intracellular forces and enhancing malignant characteristics of tumors. Compressive stress promoted cancer growth in vivo in a Rho-ROCK\u2013dependent manner. Silencing Piezo1 abolished compression-induced Rho-ROCK activation and tumor progression in this model. Accordingly, elevated PIEZO1 is associated with 35% poorer survival of patients with breast cancer. We show that acute compressive forces engender epigenetic mechanical memory via Piezo1-activated Rho-ROCK signaling, promoting tumor growth in vivo. Compressive stress promoted ROCK-dependent histone modifications associated with open chromatin, including acetylation of key histone 3\u2013lysine residues, regulating the expression of cancer-related genes across cell, explant, and in vivo tumor models. Our observations suggest that the PIEZO1-RHO-ROCK axis links tissue-level forces to persistent tumor-promoting epigenetic changes and merits evaluation as a mechanotherapy target in cancer.<\/jats:p>","DOI":"10.1126\/sciadv.aeb1271","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:58:52Z","timestamp":1772650732000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Compressive stress\u2013driven Piezo1 activation and Rho-ROCK mechanotransduction promote tumor progression via epigenetic mechanical memory"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-9285","authenticated-orcid":true,"given":"Sarah T.","family":"Boyle","sequence":"first","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-7835","authenticated-orcid":true,"given":"David","family":"Gallego-Ortega","sequence":"additional","affiliation":[{"name":"University of Technology Sydney, Ultimo, NSW 2007, Australia."},{"name":"University of New South Wales, Sydney, NSW 2052, Australia."},{"name":"Garvan Institute of Medical Research, Sydney, NSW 2010, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-9318","authenticated-orcid":true,"given":"Emmanuelle","family":"Cognard","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."},{"name":"Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3053-8509","authenticated-orcid":true,"given":"M. Zahied","family":"Johan","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."},{"name":"Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-1203","authenticated-orcid":true,"given":"Zahra","family":"Esmaeili","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."},{"name":"Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1438-0783","authenticated-orcid":true,"given":"Makoto","family":"Kamei","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."},{"name":"Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-6093","authenticated-orcid":true,"given":"Kate","family":"Poole","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-6379","authenticated-orcid":true,"given":"Michael S.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biology, SA Pathology and Adelaide University, Adelaide, SA 5000, Australia."},{"name":"Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2016.1173771"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.024166"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-73119-9_19"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2021.11.008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42382-4"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.02.007"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.05.008"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.11.026"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606743"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2017.1413496"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.05.014"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168019"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.026"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.12.3.954-961.1992"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-012-0500-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23797"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.34.20246"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37385"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep08364"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16041"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414298111"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/membranes12020237"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221958120"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21074"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi200770q"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.09.030"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1629"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22831"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718177115"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8405"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601045R"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-018-2926-7"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9329"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-022-02804-y"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.2319\/123113-955.1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.25527"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103332"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2764"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1476-5586(04)80047-2"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-0523-y"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.07.014"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00134.2005"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.12.002"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09823"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07369"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04405-3"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.02.001"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep33132"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-0747"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.09.009"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-02-0119"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200320530"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000880"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-019-02412-z"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2023.03.004"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.033"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.154"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-020-03265-z"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00870-y"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.06.025"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0749-y"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2589"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep36289"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05611-8"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0387-5"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm301098e"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004632"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1ib00043h"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213353109"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b07499"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193270"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10812"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4520"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-0859"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-09549-z"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01844-3"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-03-0106"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00360-w"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00599.2020"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12860-021-00401-6"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118910109"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E22-07-0266"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109293"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.09.012"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E22-10-0469"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104978"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep16895"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E18-04-0256"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100424"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-022-01431-x"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12987"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.05.021"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.046"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043117"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152885"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26161"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105093"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0592-0"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2024.03.032"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.66"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017143"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeb1271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:01:12Z","timestamp":1773943272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeb1271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":102,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,3,6]]}},"alternative-id":["10.1126\/sciadv.aeb1271"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeb1271","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"assertion":[{"value":"2025-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeb1271"}}