Deregulation of FoxM1b leads to tumour metastasis.
Deregulation of FoxM1b leads to tumour metastasis.
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DOI：
10.1002/emmm.201000107
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发表时间：
2011-01
影响因子：
11.1
通讯作者：
Raychaudhuri, Pradip
中科院分区：
文献类型：
--
作者：
Park, Hyun Jung;Gusarova, Galina;Wang, Zebin;Carr, Janai R.;Li, Jing;Kim, Ki-Hyun;Qiu, Jin;Park, Yoon-Dong;Williamson, Peter F.;Hay, Nissim;Tyner, Angela L.;Lau, Lester F.;Costa, Robert H.;Raychaudhuri, Pradip
关键词：
叉头框M1 b（FoxM 1b）转录因子在人类癌症中过表达，其表达通常与预后不良相关。以前，使用条件性敲除菌株，我们表明FoxM 1b是肝细胞癌（HCC）发展所必需的。然而，FoxM 1b的过度表达对HCC进展的影响很小。在这里，我们研究了FoxM 1b表达的影响，在其抑制剂Arf的情况下。我们发现，在Arf-空背景下FoxM 1b的转基因表达驱动肝纤维化和HCC的转移。我们确定了FoxM 1b参与上皮-间充质转化、细胞运动、侵袭和转移前小生境形成的新机制。FoxM 1b激活Akt-Snail 1通路并刺激Stathmin、赖氨酰氧化酶、赖氨酰氧化酶样-2和其他几个参与转移的基因的表达。此外，我们表明，Arf衍生的肽，抑制FoxM 1b，阻碍FoxM 1b表达的肝癌细胞的转移。观察结果表明，FoxM 1b是一种有效的肿瘤转移激活剂，Arf介导的FoxM 1b抑制是抑制肿瘤转移的关键机制。
The forkhead box M1b (FoxM1b) transcription factor is over-expressed in human cancers, and its expression often correlates with poor prognosis. Previously, using conditional knockout strains, we showed that FoxM1b is essential for hepatocellular carcinoma (HCC) development. However, over-expression of FoxM1b had only marginal effects on HCC progression. Here we investigated the effect of FoxM1b expression in the absence of its inhibitor Arf. We show that transgenic expression of FoxM1b in an Arf-null background drives hepatic fibrosis and metastasis of HCC. We identify novel mechanisms of FoxM1b that are involved in epithelial–mesenchymal transition, cell motility, invasion and a pre-metastatic niche formation. FoxM1b activates the Akt-Snail1 pathway and stimulates expression of Stathmin, lysyl oxidase, lysyl oxidase like-2 and several other genes involved in metastasis. Furthermore, we show that an Arf-derived peptide, which inhibits FoxM1b, impedes metastasis of the FoxM1b-expressing HCC cells. The observations indicate that FoxM1b is a potent activator of tumour metastasis and that the Arf-mediated inhibition of FoxM1b is a critical mechanism for suppression of tumour metastasis.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
DOI：
10.1073/pnas.0409722102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Campbell, JS;Hughes, SD;Fausto, N
通讯作者：
Fausto, N
影响因子：
8
作者：
Kalinina, OA;Kalinin, SA;Adami, GR
通讯作者：
Adami, GR
影响因子：
50.3
作者：
Baldassarre, G;Belletti, B;Colombatti, A
通讯作者：
Colombatti, A