{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:00:42Z","timestamp":1776852042647,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The hepatitis B virus X protein (HBx) is a central oncogenic driver in hepatocellular carcinoma (HCC). Although glypican\u20103 (GPC3) is a phosphatidylinositol proteoglycan\u2010specific biomarker for HCC. However, the combined role of HBx and GPC3 in mediating HCC cell evasion from macrophage phagocytosis remains unclear. Here, we demonstrate that HBx modulates macrophage phagocytosis by regulating GPC3 membrane morphology. Analysis of tissues from 30 patients with hepatocellular carcinoma revealed concomitant upregulation of HBx and GPC3 in tumour specimens. Mechanistically, HBx alters ERK site phosphorylation, thereby influencing the enzymatic activity of Furin protease\u2014which cleaves GPC3\u2014and consequently orchestrating morphological changes of membrane\u2010associated GPC3. To functionally validate this, THP\u20101 cells were polarized to M1 macrophages and co\u2010cultured with HCC cells. Notably, HBx directly impaired macrophage phagocytosis of HCC cells, an effect mediated through GPC3 morphological dynamics. Collectively, these findings indicate that HBx suppresses macrophage phagocytosis of HCC cells by remodelling membrane\u2010associated GPC3.<\/jats:p>","DOI":"10.1111\/jcmm.71122","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:52:37Z","timestamp":1775800357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HBx<\/scp>\n                    Induces the Production of N\u2010\n                    <scp>GPC3<\/scp>\n                    in Hepatoma Cells to Promote the Evasion of Macrophage Phagocytosis Through Activating Furin"],"prefix":"10.1111","volume":"30","author":[{"given":"Jiaying","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjiu","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1815-826X","authenticated-orcid":false,"given":"Yuli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine, Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoquan","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine, Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongzheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengsen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine, Ministry of Education, and Hainan Provincial Key Laboratory of Carcinogenesis and Intervention Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianghui","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Surgery The First Affiliated Hospital, Hainan Medical University  Haikou Hainan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.puhe.2020.09.003"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02048"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.079"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwu038"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102017\u2010314904"},{"issue":"1","key":"e_1_2_13_8_1","first-page":"338","article-title":"Hepatitis B Virus X Protein Sensitizes Hepatocellular Carcinoma Cells to Cytolysis Induced by E1B\u2010Deleted Adenovirus Through the Disruption of p53 Function","volume":"9","author":"Hsieh J. L.","year":"2003","journal-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201020\u20101312"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)32598\u20108"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010022\u201005723\u2010x"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402\u2010017\u20100364\u20102"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2022.09.011"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070511"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21455"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.122.265171"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010025\u201006106\u20100"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201003\u20102191"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwh038"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1998.0438"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902724"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478\u20103231.2008.01968.x"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2006.06.002"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40820\u2010020\u201000531\u20100"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9nr03374b"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011911\u20105"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.04.004"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201015\u20101330"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079\u2010017\u20100407\u20105"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903874"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11040741I"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1081572"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010022\u201000620\u20106"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108031"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1103149"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.005"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349\u20107006.2003.tb01430.x"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2011.26.2.214"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010001408"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102240"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1807315"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121623109"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71122","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.71122","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.71122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:13:25Z","timestamp":1776849205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.71122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/jcmm.71122"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.71122","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71122"}}