{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:30:35Z","timestamp":1781825435489,"version":"3.54.5"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T00:00:00Z","timestamp":1657411200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>It is interesting that high iron is an independent inducer or cofactor of hepatocellular carcinoma (HCC) while the amount of iron is decreased in the liver tumor tissues. Due to the previous findings that iron deficiency promoted HCC metastasis, it is of significance to identify the underlying mechanism of iron deficiency in HCC. The tumor iron content and expressions of iron\u2010metabolic molecules were observed in the primary liver cancers of rats and mice. The molecules that changed independently of iron were identified by comparing the expression profiles in the human HCC tissues and iron\u2010deprived HCC cells. The downstream effects of these molecules on regulating intracellular iron content were investigated <jats:italic toggle=\"yes\">in vitro<\/jats:italic> and further validated <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Both in primary liver cancers of rats and mice, we confirmed the decreased iron content in tumor tissues and the altered expressions of iron\u2010metabolic molecules, including transferrin receptor 1 (TfR1), six\u2010transmembrane epithelial antigen of prostate 3 (STEAP3), divalent metal transporter 1 (DMT1), SLC46A1, ferroportin, hepcidin, and ferritin. Among these, STEAP3, DMT1, and SLC46A1 were altered free of iron deficiency. However, only silence or overexpression of SLC46A1 controlled the intracellular iron content of HCC cells. The interventions of STEAP3 or DMT1 could not change the intracellular iron content. Lentivirus\u2010mediated regain of SLC46A1 expression restored the iron content in orthotopically implanted tumors, with correspondingly changes in the iron\u2010metabolic molecules as iron increasing. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Taken together, these results suggest that the loss of SLC46A1 expression leads to iron deficiency in liver tumor tissues, which would be an effective target to manage iron homeostasis in HCC.<\/jats:p>","DOI":"10.1002\/hep4.2031","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T06:14:42Z","timestamp":1657520082000},"page":"2914-2924","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["Loss of SLC46A1 decreases tumor iron content in hepatocellular carcinoma"],"prefix":"10.1097","volume":"6","author":[{"given":"Dongyao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"},{"name":"Department of Nutrition,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1247-0475","authenticated-orcid":false,"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changquan","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine,Changhai Hospital,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-8928","authenticated-orcid":false,"given":"Yuxiao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Nutrition,Second Military Medical 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