ArticleInternational journal of molecular sciences2026
Pancreatic Adenocarcinoma Up-Regulated Factor Promotes Epithelial-Mesenchymal Transition and Lung Metastasis in Hepatocellular Carcinoma.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Pancreatic adenocarcinoma upregulated factor (PAUF), a novel secreted protein highly expressed in pancreatic ductal adenocarcinoma, also influences cell invasiveness, motility, and proliferation in several cancer types. Transforming growth factor-beta (TGF-β)-induced PAUF expression enhances cancer cell migration and invasion in pancreatic ductal adenocarcinoma through mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) activation; however, the roles of PAUF in regulating epithelial-mesenchymal transition (EMT) and promoting lung metastasis in hepatocellular carcinoma (HCC) remain unclear. Thus, we investigated the regulatory mechanisms and functional roles of TGF-β-induced PAUF expression in the HCC cell lines HepG2 and Huh-7, which showed high and low expression of intact TGF-β type I and II receptors, respectively. We found that TGF-β-induced PAUF expression is mediated through the activation of the TGF-β type I/II receptor-Smads signaling pathway and that PAUF promotes EMT-associated migration and invasion by stimulating the MEK-ERK signaling cascade. In vivo studies further demonstrated that PAUF plays a critical role in lung metastatic potential, as PAUF knockdown HepG2 cells exhibited markedly reduced pulmonary metastasis, whereas PAUF-overexpressing Huh-7 cells showed substantially enhanced lung metastasis. This study identifies PAUF as a critical promoter of lung metastatic potential in HCC cells and a potential therapeutic target for HCC.
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