{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:45:31Z","timestamp":1781901931559,"version":"3.54.5"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100014673","name":"Menzies Health Institute Queensland","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100014673","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Polarity defects are frequently involved in liver diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). It was reported that vacuolar protein sorting 33B (Vps33b) plays critical roles in the maintenance of hepatocyte polarity; however, the functional roles and mechanisms of Vps33b in HCC occurrence and progression remain unknown. First of all, we showed that Vps33b is down\u2010regulated in human and mouse liver cancer samples, and the low expression levels of Vps33b correlate with the poor prognosis of many HCC patients. Liver\u2010specific Vps33b deficiency induces liver damage, progressive hepatitis, fibrosis, and HCC in male mice, indicating that Vps33b is a crucial contributory factor to hepatocarcinogenesis. <jats:italic toggle=\"yes\">Vps33b<\/jats:italic> deficiency\u2013caused liver damage was primarily due to the disorders of structural and functional hepatocyte polarity, which were reflected by the decreased protein levels of E\u2010cadherin because of inaccurate location to lysosomes and polarity defects at both apical and lateral plasma membrane proteins. The results of a mechanism study revealed that Vps33b interacts with VPS33B\u2010interacting protein, which is involved in polarity and apical protein restriction; vesicle\u2010trafficking protein Sec22b; and Flotillin\u20101 in hepatocytes and is in charge of the normal distribution of polarity\u2010determined proteins. Expression levels of Vps33b negatively correlated with the degree of inflammatory cell infiltration in livers from diethylnitrosamine\u2010induced or transgenic HCC mouse models, and the inflammatory stimuli suppressed the expression of Vps33b <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Down\u2010regulation of Vps33b expression is a critical step for inflammation\u2010driven HCC, and Vps33b serves as an important tumor suppressor in hepatocarcinogenesis.<\/jats:p>","DOI":"10.1002\/hep.30077","type":"journal-article","created":{"date-parts":[[2018,5,5]],"date-time":"2018-05-05T19:45:49Z","timestamp":1525549549000},"page":"2239-2253","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Vacuolar Protein Sorting 33B Is a Tumor Suppressor in Hepatocarcinogenesis"],"prefix":"10.1097","volume":"68","author":[{"given":"Conghui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengdian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection and Immunity, Institute of Biophysics,University of Chinese Academy of Sciences,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010qiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education,Shanghai Jiao Tong University School of Medicine,Shanghai,China"},{"name":"Collaborative 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