{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:49:19Z","timestamp":1789130959399,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773139"],"award-info":[{"award-number":["81773139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013286","name":"Specialized Research Fund for the Doctoral Program of Higher Education of China","doi-asserted-by":"publisher","award":["20130162130007"],"award-info":[{"award-number":["20130162130007"]}],"id":[{"id":"10.13039\/501100013286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease\u2010free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial\u2010mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor\u2010promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor\u2010promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.\n                  <\/jats:p>","DOI":"10.1111\/cas.14925","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T05:12:00Z","timestamp":1619845920000},"page":"2753-2769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["NAD(P)HX epimerase downregulation promotes tumor progression through ROS\/HIF\u20101\u03b1 signaling in hepatocellular carcinoma"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7999-7071","authenticated-orcid":false,"given":"Bo","family":"Sun","sequence":"first","affiliation":[{"name":"Liver Cancer Laboratory Department of Surgery Xiangya Hospital Central South University Changsha 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