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In the current study, we investigated the effect of a physiologically relevant, low concentration of Cd on the regulation of liver cancer cell proliferation, steatosis, and fibrogenic\/oncogenic signaling. Exposure to low concentrations of Cd increased endogenous reactive oxygen species (ROS) production and enhanced cell proliferation in a human bipotent progenitor cell line HepaRG and hepatocellular carcinoma (HCC) cell lines. Acute exposure of Cd increased Jagged\u20101 expression and activated Notch signaling in HepaRG and HCC cells HepG2 and SK\u2010Hep1. Cd activated AKT\/mTOR signaling by increasing phosphorylation of AKT\u2010S473 and mTOR\u2010S\u20104448 residues. Moreover, a low concentration of Cd also promoted cell steatosis and induced fibrogenic signaling in HCC cells. Chronic exposure to low concentrations of Cd\u2010activated Notch and AKT\/mTOR signaling induced the expression of pro\u2010inflammatory cytokines tumor necrosis factor\u2010alpha (TNF\u03b1) and its downstream target TNF\u2010\u03b1\u2010Induced Protein 8 (TNFAIP8). RNA\u2010Seq data revealed that chronic exposure to low concentrations of Cd modulated the expression of several fatty liver disease\u2010related genes involved in cell steatosis\/fibrosis in HepaRG and HepG2 cells. Collectively, our data suggest that low concentrations of Cd modulate steatosis along with fibrogenic and oncogenic signaling in HCC cells by activating Notch and AKT\/mTOR pathways.<\/jats:p>","DOI":"10.1002\/tox.23731","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T09:19:19Z","timestamp":1672910359000},"page":"783-797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cadmium modulates steatosis, fibrosis, and oncogenic signaling in liver cancer cells by activating notch and\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    pathways"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-9399","authenticated-orcid":false,"given":"Suryakant","family":"Niture","sequence":"first","affiliation":[{"name":"Julius L. 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