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• W1954506475 abstract "// Qiongshu Li 1 , Guomu Liu 1 , Hongyan Yuan 1 , Juan Wang 1 , Yingying Guo 1 , Tanxiu Chen 1 , Ruiping Zhai 1 , Dan Shao 1 , Weihua Ni 1 , Guixiang Tai 1 1 Department of Immunology, College of Basic Medical Science, Jilin University, Changchun 130021, China Correspondence to: Guixiang Tai, e-mail: taiguixiang@163.com Keywords: MUC1, pSmad3L, pSmad3C, HCC, JNK Received: November 14, 2014      Accepted: December 16, 2014      Published: January 20, 2015 ABSTRACT Mucin1 (MUC1) is a transmembrane glycoprotein that acts as an oncogene in human hepatic tumorigenesis. Hepatocellular carcinoma (HCC) cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor beta (TGF-β) together with stimulation of its oncogenic activity as in MUC1 expressing HCC cells; however, molecular mechanisms remain largely unknown. Type I TGF-β receptor (TβRI) and c-Jun NH2-terminal kinase (JNK) differentially phosphorylate Smad3 mediator to create 2 phosphorylated forms: COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Here, we report that MUC1 overexpression in HCC cell lines suppresses TβRI-mediated pSmad3C signaling which involves growth inhibition by up-regulating p21 WAF1 . Instead, MUC1 directly activates JNK to stimulate oncogenic pSmad3L signaling, which fosters cell proliferation by up-regulating c-Myc. Conversely, MUC1 gene silencing in MUC1 expressing HCC cells results in preserved tumor-suppressive function via pSmad3C, while eliminating pSmad3L-mediated oncogenic activity both in vitro and in vivo . In addition, high correlation between MUC1 and pSmad3L/c-Myc but not pSmad3C/p21 WAF1 expression was observed in HCC tissues from patients. Collectively, these results indicate that MUC1 shifts Smad3 signaling from a tumor-suppressive pSmad3C/p21 WAF1 to an oncogenic pSmad3L/c-Myc pathway by directly activating JNK in HCC cells, suggesting that MUC1 is an important target for HCC therapy." @default.
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• W1954506475 date "2015-01-20" @default.
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• W1954506475 title "Mucin1 shifts Smad3 signaling from the tumor-suppressive pSmad3C/p21WAF1 pathway to the oncogenic pSmad3L/c-Myc pathway by activating JNK in human hepatocellular carcinoma cells" @default.
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• W1954506475 doi "https://doi.org/10.18632/oncotarget.2973" @default.
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