{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T22:00:01Z","timestamp":1776981601323,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    Hepatocellular carcinoma remains a significant threat to human health. Recent studies have found that the intake of cellular cholesterol contributes to the development and progression of hepatocellular carcinoma, although the exact mechanisms remain unclear. Our analysis of transcriptomic and proteomic databases has identified increased mRNA and protein expression levels of NPC1, a cholesterol intracellular transporter protein, in hepatocellular carcinoma tissues. This increase is significantly associated with a worse prognosis for patients. To corroborate these findings, we performed immunohistochemical staining of NPC1 on liver tissue samples from patients, revealing significantly higher expression levels of NPC1 in hepatocellular carcinoma tissues compared to normal tissues. Subsequent investigations have revealed that NPC1 expression does not significantly influence the proliferation of hepatocellular carcinoma cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    . However, it has a substantial inhibitory effect on the progression of hepatocellular carcinoma tumors when observed\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Utilizing flow cytometry to monitor cellular changes within the tumor microenvironment has led us to discover that NPC1 plays a crucial role in the regulation of neutrophil recruitment within the tumor. Using further neutrophil depletion experiments, we determined that the role of NPC1 in advancing hepatocellular carcinoma progression truly relies on neutrophils. These observations are further reinforced by a comprehensive analysis of clinical databases alongside immunohistochemistry findings. In conclusion, our research suggests that NPC1's overexpression could contribute to hepatocellular carcinoma progression by promoting neutrophil recruitment, positioning NPC1 as a promising new biomarker and therapeutic target for hepatocellular carcinoma.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13951","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:40:10Z","timestamp":1734741610000},"page":"661-673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>NPC1<\/scp>\n                    promotes the progression of hepatocellular carcinoma by mediating the accumulation of neutrophils into the tumor microenvironment"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2434-5425","authenticated-orcid":false,"given":"Songhai","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Department of General Surgery The First People's Hospital of Hefei  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2874-2751","authenticated-orcid":false,"given":"Fubao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.014"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9090127"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32740"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0987-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.052"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.019"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2017-00176"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39733-6"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12152-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137206"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e11-04-0332r"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1872962"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2015.0121"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.050385"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30837"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62382"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.089482"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.01.007"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12177"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12010122"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77632-5"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05400-x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2022.01.001"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.181006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.708735"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00568-5"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0054-z"},{"key":"e_1_2_11_31_1","article-title":"Tumor\u2010associated neutrophils induce apoptosis of non\u2010activated CD8 T\u2010cells in a TNFalpha and NO\u2010dependent mechanism, promoting a tumor\u2010supportive environment","volume":"6","author":"Michaeli J","year":"2017","journal-title":"Onco Targets Ther"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2021.01.012"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.11.007"},{"key":"e_1_2_11_34_1","first-page":"421","article-title":"Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer","volume":"20","author":"Feng M","year":"2023","journal-title":"Cancer Biol Med"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12345"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216208"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188394"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0190-7"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM118.004165"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag1417"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04584-y"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106871"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.164459"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2007.00640.x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.03.043"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100813"},{"key":"e_1_2_11_47_1","first-page":"2281","article-title":"Niemann\u2013Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking","volume":"118","author":"Zhang JR","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6503"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-811851"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13951","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T22:00:27Z","timestamp":1743717627000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.13951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/2211-5463.13951"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.13951","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v4\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v4\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/2211-5463.13951\/v4\/decision1","asserted-by":"object"}]},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]},"assertion":[{"value":"2024-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}