Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.
Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.
复制标题
Visfatin通过诱导EMT机制参与促进结直肠癌恶变
DOI：
10.18632/oncotarget.8615
复制
发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Yang J;Zhang K;Song H;Wu M;Li J;Yong Z;Jiang S;Kuang X;Zhang T
内脂素是一种新发现的肥胖诱导的脂肪细胞因子，与肿瘤的恶性程度及预后密切相关。但其对结直肠癌（CRC）进展的影响和机制尚不清楚。我们的临床资料显示，visfatin蛋白在87例大肠癌患者中过度表达，阳性表达与淋巴结转移、高级别肿瘤和不良预后相关。血浆内脂素水平在IV期结肠癌中显著上调。内脂素可通过诱导大肠癌细胞的上皮间质转化（EMT），显著促进大肠癌细胞的体外迁移和侵袭。它可以增加调控EMT的关键转录因子Snail的表达和核转位。而Snail基因沉默则减弱内脂素诱导的EMT。进一步的研究表明内脂素可以抑制Snail与GSK-3β的结合，从而抑制Snail的泛素化。此外，内脂素还能增加β-catenin的表达和核转位，提高其与Snail启动子的结合，进而增加Snail的转录。而PI 3 K/Akt抑制剂LY 294002则可阻断内脂素诱导的Snail、波形蛋白（Vim）、β-catenin和磷酸化GSK-3β的表达上调。总之，我们的数据表明内脂素表达增加与结直肠癌患者更具侵袭性的表型相关。它可以通过Akt/GSK-3β/β-catenin信号触发CRC细胞的EMT。
Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.
登录
查看更多内容
影响因子：
--
作者：
Mishra P;Senthivinayagam S;Rana A;Rana B
通讯作者：
Rana B
影响因子：
10.8
作者：
Adya, Raghu;Tan, Bee K.;Randeva, Harpal S.
通讯作者：
Randeva, Harpal S.
组蛋白脱乙酰酶抑制剂通过上调 Snail 诱导上皮间质转化促进癌症进展
DOI：
10.1016/j.bbamcr.2012.12.002
发表时间：
2013-03-01
影响因子：
5.1
作者：
Jiang, Guan-Min;Wang, Hong-Sheng;Du, Jun
通讯作者：
Du, Jun
影响因子：
--
作者：
Park HJ;Kim SR;Kim SS;Wee HJ;Bae MK;Ryu MH;Bae SK
通讯作者：
Bae SK
影响因子：
2.4
作者：
Li, Yan;Li, Xun;Zhu, Yu
通讯作者：
Zhu, Yu