{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:58:40Z","timestamp":1790416720502,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52273301"],"award-info":[{"award-number":["52273301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52473145"],"award-info":[{"award-number":["52473145"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52333004"],"award-info":[{"award-number":["52333004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52131302"],"award-info":[{"award-number":["52131302"]}],"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 Materials"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cuproptosis has recently been identified as a novel metabolic cell death pathway that holds great promise for cancer therapy. However, cuproptosis resistance developed by tumor cells severely impairs its anticancer efficacy. Here, our study uncovers that the FAK\u2010YAP signaling axis in tumor cells plays important roles in the development of cuproptosis resistance and the promotion of tumor stemness. To therapeutically target this signaling axis, a CRISPR\u2010cuproptosis synergistic nanoplatform (CPLNP@HA) is elaborately designed for targeted co\u2010delivery of a Ptk2 (encoding FAK) CRISPR\u2010Cas9 knockout plasmid to block FAK\u2010YAP signaling axis and Cu\u2010elesclomol (Cu\u2010ES, a cuproptosis inducer) into tumor cells. Mechanistically, CPLNP@HA efficiently silences FAK expression, which subsequently blocks the cuproptosis\u2010induced activation of the FAK\u2010YAP signaling cascade. This intervention not only sustains intracellular copper accumulation to reinforce cuproptosis but also reduces tumor stemness, thereby significantly potentiating the therapeutic outcomes of cuproptosis and activating tumoricidal immunity as evidenced by transcriptomic analysis. In combination with immune checkpoint blockade therapy, CPLNP@HA markedly inhibits tumor development upon rechallenge after surgical resection. Our work establishes FAK\u2010YAP signaling axis as a new therapeutic target to overcome cuproptosis resistance and inhibit tumor stemness, providing a promising combinatorial paradigm to sensitize tumor to cuproptosis and immunotherapy.<\/jats:p>","DOI":"10.1002\/adma.75155","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:15:10Z","timestamp":1790414110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting FAK\u2010YAP Signaling Axis Inhibits Tumor Stemness and Overcomes Tumor Resistance to Cuproptosis"],"prefix":"10.1002","author":[{"given":"Hao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Zhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9796-5337","authenticated-orcid":false,"given":"Shi\u2010Man","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Xin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3100-2319","authenticated-orcid":false,"given":"Wei\u2010Hai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-6005","authenticated-orcid":false,"given":"Xian\u2010Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongnan Hospital &amp; Key Laboratory of Biomedical Polymers of Ministry of Education &amp; Department of Chemistry Wuhan University  Wuhan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010024\u201000876\u20100"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010026\u201002607\u20106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202511993"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318431110"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CS00083A"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.11.046"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202500337"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408106"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054469\u20107"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102022\u2010327430"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010023\u201001732\u2010y"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001229\u2010y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002192\u20100"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.02.015"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201081317\u2010x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010025\u201002529\u2010x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.805"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.027"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz8899"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010021\u201000822\u20107"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010023\u201001744\u20108"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27320"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201016\u20103152"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201019\u20100860"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201061795\u2010x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010020\u20100558\u20104"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010020\u20100370\u20101"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523\u2010021\u201000313\u2010w"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3319"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010022\u201002258\u20101"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202200999"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102021\u2010325564"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2023.110956"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.04.026"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010014\u20101823\u2010z"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001453\u20100"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3461"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/sstr.202500676"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.382"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtherbio.2023.103624"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102010\u201010\u2010313296"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010021\u201000340\u20106"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.01.009"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.03.023"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.06.016"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010025\u201004029\u20103"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.04.004"}],"container-title":["Advanced Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75155","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adma.75155","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adma.75155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:15:12Z","timestamp":1790414112000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adma.75155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,26]]},"references-count":48,"alternative-id":["10.1002\/adma.75155"],"URL":"https:\/\/doi.org\/10.1002\/adma.75155","archive":["Portico"],"relation":{},"ISSN":["0935-9648","1521-4095"],"issn-type":[{"value":"0935-9648","type":"print"},{"value":"1521-4095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,26]]},"assertion":[{"value":"2026-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e75155"}}