http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Lim, Seung-Oe,Park, Sung-Gyoo,Yoo, Jun-Hi,Park, Young-Min,Kim, Hie-Joon,Jang, Kee-Taek,Cho, Jae-Won,Yoo, Byung-Chul,Jung, Gu-Hung,Park, Cheol-Keun WJG Press 2005 World journal of gastroenterology Vol.11 No.14
<P>Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)-related HCC.</P>
Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma
Lim, Seung-Oe,Kim, Hongtae,Jung, Guhung Elsevier 2010 FEBS letters Vol.584 No.11
<P><B>Abstract</B></P><P>The tumor suppressor protein p53 is a key regulator of cell cycle arrest and apoptosis. Snail protein regulates cancer-associated malignancies. However, the relationship between p53 and Snail proteins in hepatocellular carcinoma (HCC) has not been completely understood. To determine whether Snail and p53 contribute to hepatocarcinogenesis, we analyzed the expression of Snail proteins in p53-overexpressing HCC cells. We found that p53 wild-type (WT) induced the degradation of Snail protein via murine double minute 2-mediated ubiquitination, whereas p53 mutant did not induce Snail degradation. As we expected, only p53WT induced endogenous Snail protein degradation and inhibited tumor cell invasion. These findings contribute to a better understanding of the role of p53 mutation and Snail overexpression as a late event in hepatocarcinogenesis.</P><P><B>Structured summary</B></P><P>MINT-7718917: <I>p53</I> (uniprotkb:P04637) <I>physically interacts</I> (MI:0915) with <I>Snai1</I> (uniprotkb:O95863) by <I>anti bait coimmunoprecipitation</I> (MI:0006)</P><P>MINT-7719877: <I>Snai1</I> (uniprotkb:O95863) <I>physically interacts</I> (MI:0915) with <I>ubiquitin</I> (uniprotkb:P62988) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7718928: <I>Snai1</I> (uniprotkb:O95863) <I>physically interacts</I> (MI:0915) with <I>p53</I> (uniprotkb:P04637) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7718939: <I>Snai1</I> (uniprotkb:O95863) <I>physically interacts</I> (MI:0915) with <I>MDM2</I> (uniprotkb:Q00987) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P>
Lim, Seung‐,Oe,Park, Young Min,Kim, Hyeon Seop,Quan, Xiaoyuan,Yoo, Jeong Eun,Park, Young Nyun,Choi, Gi Hong,Jung, Guhung Wiley Subscription Services, Inc., A Wiley Company 2011 Hepatology Vol.53 No.4
<P><B>Abstract</B></P><P>The tumor suppressor p53 is a key prognostic factor in hepatocellular carcinoma (HCC), yet only 35% of grade III tumors exhibit mutation of p53. Several other pathways have been implicated in HCC and, among these, the role of the Notch1/Snail pathway remains unclear. Therefore, we investigated the expression of p53, Notch1, and Snail proteins in HCC with regard to both clinical grade and p53 mutational status. Immunoblotting for p53 revealed that, whereas in many tumors increased p53 was a result of p53 mutation, wildtype p53 (p53WT) expression was also frequently elevated in HCCs. Coordinated evaluation of p53, Notch1, and Snail expression suggests that grade III HCC can be subdivided based on the expression of these three proteins. We found that Notch1 expression in HCC tissues and cell lines is differentially affected by p53WT and mutant p53 (p53Mut). Notch1 expression was correlated with p53 expression in cells expressing p53WT, but was not elevated in p53Mut‐expressing cells. Virally mediated expression or silencing of p53WT or p53Mut confirmed that p53WT overexpression causes Notch1 up‐regulation in HCC. Surprisingly, the consequence of Notch1 overexpression for the proliferative and invasive capacity of HCC cells depends on both the p53 mutational status and activation of the Snail pathway. <I>Conclusion:</I> In the presence of p53WT, Snail/Notch1 activation increased the invasiveness of HCC cells. In contrast, in the absence of p53WT, Notch1 decreased the invasiveness of HCC. Taken together, these findings shed new light on the complex role of the Notch1/Snail axis in HCC and provide a framework for further classifying HCC based on the expression and mutational status of p53 and the expression of Notch1 and Snail. (H<SMALL>EPATOLOGY</SMALL> 2011;53:1352‐1362)</P>