PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2.
PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2.
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PLZF通过调节IFIT2抑制胆囊癌的增殖和转移
DOI：
10.1038/s41419-017-0107-3
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发表时间：
2018-01-22
影响因子：
9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Shen H;Zhan M;Zhang Y;Huang S;Xu S;Huang X;He M;Yao Y;Man M;Wang J
胆囊癌是一种预后极差的恶性肿瘤。尽管早幼粒细胞白血病锌指蛋白（zinc-finger protein， PLZF）在许多癌症中被报道失调且与临床预后相关，但其在GBC进展中的作用却鲜为人知。在这项研究中，我们发现PLZF在GBC中的表达降低，与TNM晚期、远处转移和较短的总生存期有关。此外，异位PLZF在GBC细胞（NOZ和GBC- sd）中的表达显著降低了细胞的增殖、迁移和侵袭。在异种移植小鼠模型中，PLZF过表达可以抑制肿瘤生长和肝转移。力学研究证实PLZF可以调节GBC细胞系细胞周期阻滞相关基因p21和上皮-间质转化（epithelial-mesenchymal transition， EMT）相关基因（E-cadherin和N-cadherin）的表达。重要的是，PLZF通过增加STAT1蛋白水平显著增加干扰素诱导的四肽重复2 （IFIT2）蛋白的mRNA转录，STAT1蛋白是参与肿瘤进展的已知因子。此外，消融PLZF过表达细胞中的IFIT2，至少部分地破坏了PLZF的肿瘤抑制功能，导致肿瘤生长和EMT程序受损。这些研究表明PLZF通过调节IFIT2抑制增殖和转移。综上所述，我们的研究表明PLZF可能是一种有前景的GBC肿瘤生物标志物，也是一种潜在的治疗靶点。
Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated in numerous cancers and also relevant to clinical prognosis, its role in GBC progression has been little known. In this study, we found PLZF expression was decreased in GBC, correlating to advanced TNM stage, distant metastasis, and shorter overall survival. Moreover, ectopic PLZF expression in GBC cells (NOZ and GBC-SD) significantly reduced the cell proliferation, migration, and invasion. Consistently, overexpression of PLZF in xenograft mice model could suppress tumor growth and liver metastasis. Mechanical investigations verified PLZF could regulate the expression of cell cycle arrest-associated gene p21 and epithelial–mesenchymal transition (EMT)-related genes (E-cadherin and N-cadherin) in GBC cell lines. Importantly, PLZF remarkably increased the mRNA transcription of interferon-induced protein with tetratricopeptide repeat 2 (IFIT2) by increasing STAT1 protein level, a known factor involved in tumor progression. Furthermore, ablation of IFIT2 in PLZF overexpression cells abrogated the tumor-suppressive function of PLZF, at least partially, leading to impaired tumor growth and EMT program. These studies indicated PLZF inhibited the proliferation and metastasis via regulation of IFIT2. In conclusion, our study demonstrated PLZF could be a promising tumor biomarker for GBC, and also be a potential therapeutic target.
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DOI：
10.1016/j.biocel.2007.07.011
发表时间：
2007-01-01
影响因子：
4
作者：
Guarino, Marcello
通讯作者：
Guarino, Marcello
PLZF 介导 PTEN/AKT/FOXO3a 信号传导抑制前列腺肿瘤发生。
影响因子：
3.7
作者：
Cao J;Zhu S;Zhou W;Li J;Liu C;Xuan H;Yan J;Zheng L;Zhou L;Yu J;Chen G;Huang Y;Yu Z;Feng L
通讯作者：
Feng L
DOI：
10.1073/pnas.1304318110
发表时间：
2013-07-09
影响因子：
11.1
作者：
Jin, Yang;Qu, Su;Saatcioglu, Fahri
通讯作者：
Saatcioglu, Fahri
影响因子：
3.8
作者：
Feng X;Wang Y;Ma Z;Yang R;Liang S;Zhang M;Song S;Li S;Liu G;Fan D;Gao S
通讯作者：
Gao S
影响因子：
3.3
作者：
Li, X;Hui, AM;Makuuchi, M
通讯作者：
Makuuchi, M