title: Critical roles of p53 in epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the biggest obstacle in curing HCC is its high metastasis potential. Alteration of p53 is the most frequent genetic change found in HCC. Although the biological function of p53 in tumor initiation and progression has been well characterized, whether or not p53 is implicated in metastasis of HCC is largely unknown. In this study, we analyzed the potential functions of p53 in epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Both insulin- and TGF-β1-induced changes of critical EMT markers were greatly enhanced by p53 knockdown in HCC cells. The insulin- and TGF-β1-stimulated migration of HCC cells were enhanced by p53 knockdown. Furthermore, in vivo metastasis of HCC cells using different mouse models was robustly enhanced by p53 knockdown. In addition, we found that p53 regulation on EMT and metastasis involves β-catenin signaling. The nuclear accumulation and transcriptional activity of β-catenin was modulated by p53. The enhanced EMT phenotype, cell migration and tumor metastasis of HCC cells by p53 knockdown were abrogated by inhibiting β-catenin signal pathway. In conclusion, this study reveals that p53 plays a pivotal role in EMT and metastasis of HCC cells via its regulation on β-catenin signaling.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Jiang
authors.forename: Dongxian
authors.initials: D
authors.lastname: Guan
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Hongkun
authors.initials: H
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
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