{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:41:40Z","timestamp":1791042100323,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T00:00:00Z","timestamp":1411776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31230005"],"award-info":[{"award-number":["31230005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81171525"],"award-info":[{"award-number":["81171525"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Hepatitis B virus (HBV) infection is one of the major causes of acute and chronic liver diseases, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCC accounts for more than 85% of primary liver cancers and is the seventh most common cancer and the third leading cause of cancer\u2010related deaths. However, the mechanism by which HBV induces HCC is largely unknown. Collagen triple helixes repeat containing 1 (CTHRC1) is a secreted protein and has characteristics of a circulating hormone with potentially broad implications for cell metabolism and physiology. CTHRC1 is associated with human cancers, but its effect on HCC is unknown. Here, we revealed that CTHRC1 expression is highly correlated with HCC progression in HBV\u2010infected patients, and demonstrated that HBV stimulates CTHRC1 expression by activating nuclear factor\u2010kappa B (NF\u2010\u03baB) and cAMP response element binding protein (CREB), through extracellular signal\u2010regulated kinase\/c\u2010Jun N\u2010terminal kinase (ERK\/c\u2010JNK) pathway. In addition, CTHRC1 activates hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1) and vascular endothelial growth factor (VEGF) through regulating phosphoinosmde\u20103\u2010kinase\/protein kinase B\/mammalian target of rapamycin (PI\u20103K\/AKT\/mTOR) pathway. More interestingly, CTHRC1 enhances colony formation, migration, and invasion of hepatoma cells by regulating p53 and stimulating matrix metalloproteinase\u20109 (MMP\u20109) expression. In addition, knock\u2010down of CTHRC1 results in the repression of HBV\u2010associated carcinogenesis in nude mice. Thus, we revealed a novel mechanism by which HBV facilitates HCC development through activating the oncoprotein CTHRC1, which in turn enhances HBV\u2010related HCC progression by stimulates colony formation, migration, and invasion of hepatoma cells through regulating multiple cellular factors and signal cascades. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22229","type":"journal-article","created":{"date-parts":[[2014,9,27]],"date-time":"2014-09-27T21:29:18Z","timestamp":1411853358000},"page":"1554-1566","source":"Crossref","is-referenced-by-count":32,"title":["The collagen triple helix repeat containing 1 facilitates hepatitis B virus\u2010associated hepatocellular carcinoma progression by regulating multiple cellular factors and signal cascades"],"prefix":"10.1002","volume":"54","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences Wuhan University Wuhan 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