Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling.
Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling.
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DOI：
10.18632/oncotarget.3117
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发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Huang MC
中科院分区：
文献类型：
--
作者：
Huang MJ;Hu RH;Chou CH;Hsu CL;Liu YW;Huang J;Hung JS;Lai IR;Juan HF;Yu SL;Wu YM;Huang MC
o -糖基化是一种常见的蛋白质修饰。异常的o -糖基化与许多癌症有关。GALNT1是一种能启动蛋白o糖基化的galnac转移酶。我们发现GALNT1在肝细胞癌（HCC）中经常上调，并与较差的患者生存率相关。GALNT1过表达增加，敲低降低HCC细胞的迁移和侵袭。敲低GALNT1抑制egf诱导的迁移和侵袭。通过降低EGFR o -糖基化，GALNT1的下调降低了EGFR的激活并增加了EGFR的降解。本研究表明，下调GALNT1足以通过降低EGFR信号传导抑制HCC细胞的恶性表型。因此，GALNT1是HCC的潜在靶点。
O-glycosylation is a common protein modification. Aberrant O-glycosylation is associated with many cancers. GALNT1 is a GalNAc-transferase that initiates protein O-glycosylation. We found that GALNT1 is frequently up-regulated in hepatocellular carcinoma (HCC) and is associated with poor patient survival. Overexpression of GALNT1 increased and knockdown decreased HCC cell migration and invasion. Knockdown of GALNT1 inhibited EGF-induced migration and invasion. Knockdown of GALNT1 decreased EGFR activation and increased EGFR degradation, by decreasing EGFR O-glycosylation. This study demonstrates that down-regulation of GALNT1 is sufficient to suppress malignant phenotype of HCC cells by decreasing EGFR signaling. Thus, GALNT1 is a potential target in HCC.
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影响因子：
13.5
作者：
Fuchs, Bryan C.;Hoshida, Yujin;Fujii, Tsutomu;Wei, Lan;Yamada, Suguru;Lauwers, Gregory Y.;McGinn, Christopher M.;DePeralta, Danielle K.;Chen, Xintong;Kuroda, Toshihiko;Lanuti, Michael;Schmitt, Anthony D.;Gupta, Supriya;Crenshaw, Andrew;Onofrio, Robert;Taylor, Bradley;Winckler, Wendy;Bardeesy, Nabeel;Caravan, Peter;Golub, Todd R.;Tanabe, Kenneth K.
通讯作者：
Tanabe, Kenneth K.
影响因子：
11.5
作者：
Lau, Chi Keung;Yang, Zhen Fan;Fan, Sheung Tat
通讯作者：
Fan, Sheung Tat
影响因子：
29
作者：
Holleboom AG;Karlsson H;Lin RS;Beres TM;Sierts JA;Herman DS;Stroes ES;Aerts JM;Kastelein JJ;Motazacker MM;Dallinga-Thie GM;Levels JH;Zwinderman AH;Seidman JG;Seidman CE;Ljunggren S;Lefeber DJ;Morava E;Wevers RA;Fritz TA;Tabak LA;Lindahl M;Hovingh GK;Kuivenhoven JA
通讯作者：
Kuivenhoven JA
DOI：
10.1073/pnas.0906541106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Murphy, Jane E.;Padilla, Benjamin E.;Bunnett, Nigel W.
通讯作者：
Bunnett, Nigel W.
影响因子：
6.1
作者：
Desai, Monica Dandona;Saroya, Bikramajit Singh;Lockhart, Albert Craig
通讯作者：
Lockhart, Albert Craig