{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:46:41Z","timestamp":1790768801316,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"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":["22075127"],"award-info":[{"award-number":["22075127"]}],"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":["31972926"],"award-info":[{"award-number":["31972926"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Organophosphate flame retardants (OPFRs) have been widely used due to their unique properties. The OPFRs are mainly metabolized in the liver. However, whether the plasma level of OPFRs was involved in the progression of liver cancer remains unclear. Triphenyl phosphate (TPP) is one of the OPFRs that are mostly detected in environment. In this study, we performed CCK8, ATP, and EdU analyses to evaluate the effect of TPP at the concentrations at 0.025\u201312.8\u00a0\u03bcM on the proliferation, invasion, and migration of Hep3B, a hepatocellular carcinoma (HCC) cell line. Tumor\u2010bearing mouse model was used for in vivo validation. The results showed that low concentrations of TPP at (0.025\u20130.1\u00a0\u03bcM), which are obtained in the plasma of patients with cancers, remarkably promoted cell invasion and migration of Hep3B cells. Animal experiments confirmed that TPP treatment significantly enhanced tumor growth in the xenograft HCC model. To explore the possible molecular mechanisms that might mediate the actions of TPP on Hep3B cells, we profiled gene expression in groups treated with or without TPP at the concentrations of 0.05 and 0.1\u00a0\u03bcM using transcriptional sequencing. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein\u2013protein interaction (PPI) analyses demonstrated that pathways affected by differentially expressed genes (DEGs) were mainly in nuclear\u2010transcribed mRNA catabolic processes, cytosolic ribosome, and ATPase activity. A 0.05 and 0.1\u00a0\u03bcM TPP led to up\u2010regulation of a series of genes including <jats:italic>EREG, DNPH1, SAMD9, DUSP5, PFN1, CKB, MICAL2, SCUBE3<\/jats:italic>, and <jats:italic>CXCL8<\/jats:italic>, but suppressed the expression of MCC. These genes have been shown to be associated with proliferation and movement of cells. Taken together, our findings suggest that low concentration of TPP could fuel the proliferation, invasion, and migration of HCC cells. Thus, TPP is a risk factor in the progression of HCC in human beings.<\/jats:p>","DOI":"10.1002\/tox.23609","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T19:15:31Z","timestamp":1656702931000},"page":"2445-2459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Low concentration triphenyl phosphate fuels proliferation and migration of hepatocellular carcinoma cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Liang","family":"Ye","sequence":"first","affiliation":[{"name":"General Surgery Center, Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver Institute of Regenerative Medicine Zhujiang Hospital, Southern Medical University  Guangzhou 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