{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:03:00Z","timestamp":1790182980016,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":77,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Chongqing Innovation Leading Talent Project","award":["CQYC20220303706"],"award-info":[{"award-number":["CQYC20220303706"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"DOI":"10.1186\/s12935-026-04392-2","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:44:06Z","timestamp":1782402246000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage-derived CTSZ promotes prostate cancer progression via \u03b1V\u03b23 integrin-mediated activation of the AKT\/FOXO1\/JUNB signaling axis"],"prefix":"10.1186","volume":"26","author":[{"given":"Youxin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saipeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqian","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langlang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"4392_CR1","doi-asserted-by":"publisher","unstructured":"Siegel, R. L.; Kratzer, T. B.; Giaquinto, A. N.; Sung, H.; Jemal, A. Cancer statistics, 2025. CA Cancer J. Clin. 2025, 75(1), 10\u201345. https:\/\/doi.org\/10.3322\/caac.21871","DOI":"10.3322\/caac.21871"},{"key":"4392_CR2","doi-asserted-by":"publisher","unstructured":"Wiggins, N. S.; Nogueira, L.; DeSantis, T. P.; Miller, A. B.; Young, K. R.; Islami, F.; Jemal, A.; Anderson, R.; Goding Sauer, A.; Siegel, R. L. Cancer treatment and survivorship statistics, 2025. CA Cancer J. Clin. 2025, 75(4), 277\u2013302. https:\/\/doi.org\/10.3322\/caac.70011","DOI":"10.3322\/caac.70011"},{"key":"4392_CR3","doi-asserted-by":"publisher","unstructured":"Naderi, S.; Kozlov, M.; Tavakoli, N.; Gunter, M.; Zare, A. New frontiers in prostate cancer treatment from systemic therapy to targeted therapy. Front. Mol. Med. 2025, 17(9), 2191\u20132214. https:\/\/doi.org\/10.1038\/s44321-025-00282-8","DOI":"10.1038\/s44321-025-00282-8"},{"key":"4392_CR4","doi-asserted-by":"publisher","unstructured":"Bai, X.; Wang, W.; Aizezi, M.; Zhang, X.; Ma, W.; Sun, G.; Dong, L.; Xu, M.; Wang, X.; Tang, C.; Song, H.; Huang, X.; Zhang, C.; Zhu, Y.; Zhang, M.; Ye, D.; Wang, J. Integration Analysis of Single-Cell Multi-Omics Reveals Prostate Cancer Heterogeneity. Adv. Sci. 2024, 11(18), e2305724 https:\/\/doi.org\/10.1002\/advs.202305724","DOI":"10.1002\/advs.202305724"},{"key":"4392_CR5","doi-asserted-by":"publisher","unstructured":"Bou-Dargham, M. J.; Sha, L.; Sang, Q.-X. A.; Zhang, J. Immune landscape of human prostate cancer: immune evasion mechanisms and biomarkers for personalized immunotherapy. BMC Cancer 2020, 20(1), 572. https:\/\/doi.org\/10.1186\/s12885-020-07058-y","DOI":"10.1186\/s12885-020-07058-y"},{"key":"4392_CR6","doi-asserted-by":"publisher","unstructured":"Han, C.; Deng, Y.; Xu, W.; Liu, Z.; Wang, T.; Wang, S.; Liu, J.; Liu, X. The Roles of Tumor-Associated Macrophages in Prostate Cancer. J. Oncol. 2022, 2022, 8580043. https:\/\/doi.org\/10.1155\/2022\/8580043","DOI":"10.1155\/2022\/8580043"},{"key":"4392_CR7","doi-asserted-by":"publisher","unstructured":"Boutilier, A. J.; Elsawa, S. F. Macrophage Polarization States in the Tumor Microenvironment. Int. J. Mol. Sci. 2021, 22(13), 6995. https:\/\/doi.org\/10.3390\/ijms22136995","DOI":"10.3390\/ijms22136995"},{"key":"4392_CR8","doi-asserted-by":"publisher","unstructured":"Zhou, K.; Cheng, T.; Zhan, J.; Peng, X. Targeting tumor-associated macrophages in the tumor microenvironment (Review). Oncol. Lett. 2020, 20 (5), 234 https:\/\/doi.org\/10.3892\/ol.2020.12097","DOI":"10.3892\/ol.2020.12097"},{"key":"4392_CR9","doi-asserted-by":"publisher","unstructured":"Chanmee, T.; Ontong, P.; Konno, K.; Itano, N. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment. Cancers 2014, 6(3), 1670\u20131690. https:\/\/doi.org\/10.3390\/cancers6031670","DOI":"10.3390\/cancers6031670"},{"key":"4392_CR10","doi-asserted-by":"publisher","unstructured":"Zarif, J. C.; Baena-Del Valle, J. A.; Hicks, J. L.; Heaphy, C. M.; Vidal, I.; Luo, J.; Lotan, T. L.; Hooper, J. E.; Isaacs, W. B.; Pienta, K. J.; De Marzo, A. M. Mannose Receptor-positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic Castration-resistant Disease. Eur. Urol. Oncol. 2019, 2(4), 429\u2013436. https:\/\/doi.org\/10.1016\/j.euo.2018.09.014","DOI":"10.1016\/j.euo.2018.09.014"},{"key":"4392_CR11","doi-asserted-by":"publisher","unstructured":"Akkari, L.; Gocheva, V.; Kester, J. C.; Hunter, K. E.; Quick, M. L.; Sevenich, L.; Wang, H. W.; Peters, C.; Tang, L. H.; Klimstra, D. S. Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix. Genes Dev. 2014, 28(19), 2134\u20132150. https:\/\/doi.org\/10.1101\/gad.249599.114","DOI":"10.1101\/gad.249599.114"},{"key":"4392_CR12","doi-asserted-by":"publisher","unstructured":"Kos, J.; Vi\u017ein, T.; Fonovi\u0107, U. P.; Pi\u0161lar, A. Intracellular signaling by cathepsin X: molecular mechanisms and diagnostic and therapeutic opportunities in cancer. Semin. Cell Biol. 2015, 31, 76\u201383. https:\/\/doi.org\/10.1016\/j.semcancer.2014.05.001","DOI":"10.1016\/j.semcancer.2014.05.001"},{"key":"4392_CR13","doi-asserted-by":"publisher","unstructured":"Lines, K. E.; Chelala, C.; Dmitrovic, B.; Wijesuriya, N.; Kocher, H. M.; Marshall, J. F.; Crnogorac-Jurcevic, T. S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells. Am. J. Pathol. 2012, 180(4), 1485\u20131494. https:\/\/doi.org\/10.1016\/j.ajpath.2011.12.031","DOI":"10.1016\/j.ajpath.2011.12.031"},{"issue":"1","key":"4392_CR14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.yexcr.2004.12.006","volume":"306","author":"J Kos","year":"2005","unstructured":"Kos, J.; Sekirnik, A.; Premzl, A.; Zupanc Bergant, V.; Langerholc, T.; Repnik, U. K.; Turk, B.; Werle, B.; Golouh, R.; Jeras, M. Carboxypeptidases cathepsins X and B display distinct protein profile in human cells and tissues. Exp. Cell Res. 2005, 306(1), 103\u2013113 https:\/\/doi.org\/10.1016\/j.yexcr.2004.12.006","journal-title":"E C R"},{"key":"4392_CR15","doi-asserted-by":"publisher","unstructured":"Krueger, S.; Kalinski, T.; Hundertmark, T.; Wex, T.; K\u00fcster, D.; Peitz, U.; Ebert, M.; N\u00e4gler, D. K.; Kellner, U.; Malfertheiner, P.; Naumann, M.; R\u00f6cken, C.; Roessner, A. Up-regulation of cathepsin X in Helicobacter pylori gastritis and gastric cancer. J. Pathol. 2005, 207(1), 32\u201342. https:\/\/doi.org\/10.1002\/path.1820","DOI":"10.1002\/path.1820"},{"key":"4392_CR16","doi-asserted-by":"publisher","unstructured":"Tao, J.; Chen, Y.; Bian, X.; Cai, T.; Song, C.; Liang, C.; Hao, Z.; Meng, J.; Ge, Q.; Zhou, J. Prognostic and immunological implications of cathepsin Z overexpression in prostate cancer. Front. Immunol. 2025, 16, 1618487. https:\/\/doi.org\/10.3389\/fimmu.2025.1618487","DOI":"10.3389\/fimmu.2025.1618487"},{"key":"4392_CR17","doi-asserted-by":"publisher","unstructured":"Chen, S.; Deng, B.; Liu, Y.; Xie, L.; Xu, J.; Hu, R.; Zhao, F.; Song, G.; Ni, R.; Liu, H.; Zhou, Z.; Huang, G.; Shen, W. The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer. J. Transl. Med. 2025, 23(1), 865. https:\/\/doi.org\/10.1186\/s12967-025-06865-w","DOI":"10.1186\/s12967-025-06865-w"},{"key":"4392_CR18","doi-asserted-by":"publisher","unstructured":"Liu, F.; Wu, Q.; Dong, Z.; Liu, K. Integrins in cancer: Emerging mechanisms and therapeutic opportunities. Pharmacol. Ther. 2023, 247, 108458. https:\/\/doi.org\/10.1016\/j.pharmthera.2023.108458","DOI":"10.1016\/j.pharmthera.2023.108458"},{"key":"4392_CR19","doi-asserted-by":"publisher","unstructured":"Thomsen, M. K.; Bakiri, L.; Hasenfuss, S. C.; Wu, H.; Morente, M.; Wagner, E. F. Loss of JUNB\/AP-1 promotes invasive prostate cancer. Cell Death Differ. 2015, 22(4), 574\u2013582. https:\/\/doi.org\/10.1038\/cdd.2014.213","DOI":"10.1038\/cdd.2014.213"},{"key":"4392_CR20","doi-asserted-by":"publisher","unstructured":"Guan, H.; Peng, R.; Fang, F.; Mao, L.; Chen, Z.; Yang, S.; Dai, C.; Wu, H.; Wang, C.; Feng, N.; Xu, B.; Chen, M. Tumor-associated macrophages promote prostate cancer progression via exosome-mediated miR-95 transfer. J. Cell. Physiol. 2020, 235(12), 9729\u20139742. https:\/\/doi.org\/10.1002\/jcp.29784","DOI":"10.1002\/jcp.29784"},{"key":"4392_CR21","doi-asserted-by":"publisher","first-page":"0","DOI":"10.7150\/thno\/v01p0189","volume":"1","author":"C Kai","year":"2011","unstructured":"Chen, K.; Chen, X. Integrin targeted delivery of chemotherapeutics. Theranostics 2011, 1, 189\u2013200. https:\/\/doi.org\/10.7150\/thno\/v01p0189","journal-title":"Integrin Target delivery chemotherapeutics"},{"key":"4392_CR22","doi-asserted-by":"publisher","unstructured":"Lin, T.-H.; Lin, S.-C.; Huang, Y.-L.; Lai, C.-Y.; He, X.-Y.; Tsai, C.-H.; Fong, Y.-C.; Wu, H.-C.; Chang, A.-C.; Lin, Y.-Y.; Lin, C.-H.; Tang, C.-H. Apelin facilitates integrin \u03b1v\u03b23 production and enhances metastasis in prostate cancer by activating STAT3 and inhibiting miR-8070. Int. J. Biol. Sci. 2025, 21(9), 4117\u20134128. https:\/\/doi.org\/10.7150\/ijbs.113161","DOI":"10.7150\/ijbs.113161"},{"key":"4392_CR23","doi-asserted-by":"publisher","unstructured":"Gu, Y.; Dong, B.; He, X.; Qiu, Z.; Zhang, J.; Zhang, M.; Liu, H.; Pang, X.; Cui, Y. M. The challenges and opportunities of \u03b1v\u03b23-based therapeutics in cancer: from bench to clinical trials. Pharmacol. Res. 2023, 106694. https:\/\/doi.org\/10.1016\/j.phrs.2023.106694","DOI":"10.1016\/j.phrs.2023.106694"},{"key":"4392_CR24","doi-asserted-by":"publisher","unstructured":"Mao, X.; Li, W.; Guan, Y.; Kuai, X.; Yuan, J. COL3A1 promotes gastric cancer progression by activating PI3K\/AKT signaling. Cancer Gene Ther. 2026, 10.1038\/s41417-026-01011-0IF: 5.0 https:\/\/doi.org\/10.1038\/s41417-026-01011-0","DOI":"10.1038\/s41417-026-01011-0"},{"key":"4392_CR25","doi-asserted-by":"publisher","unstructured":"Xing, Y.-Q.; Li, A.; Yang, Y.; Li, X.-X.; Zhang, L.-N.; Guo, H.-C. The regulation of FOXO1 and its role in disease progression. Life Sci. 2018, 193, 124\u2013131. https:\/\/doi.org\/10.1016\/j.lfs.2017.11.030","DOI":"10.1016\/j.lfs.2017.11.030"}],"container-title":["Cancer Cell International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04392-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04392-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04392-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:04:25Z","timestamp":1789041865000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12935-026-04392-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4392"],"URL":"https:\/\/doi.org\/10.1186\/s12935-026-04392-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8466350\/v1","asserted-by":"object"}]},"ISSN":["1475-2867"],"issn-type":[{"value":"1475-2867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"assertion":[{"value":"28 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The human study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. The tumor tissue microarray of patients with PCa used in this study was provided by Changsha Yaxiang Biotechnology Co., Ltd. This study was reviewed and approved by the Ethics Committee of the company (ethics approval number Csyayj2024022). The animal study was approved by the Animal Experiment Welfare and Ethics Committee of Army Medical University (AMUWEC20232943). All animal experiments were conducted in compliance with the requirements of Chinese microbiology.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"306"}}