Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
Nuclear Janus-Activated Kinase 2/Nuclear Factor 1-C2 Suppresses Tumorigenesis and Epithelial-to-Mesenchymal Transition by Repressing Forkhead Box F1
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DOI：
10.1158/0008-5472.can-09-1677
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发表时间：
2010-03-01
期刊：
影响因子：
11.2
通讯作者：
Kannius-Janson, Marie
中科院分区：
文献类型：
--
作者：
Nilsson, Jeanette;Helou, Khalil;Kannius-Janson, Marie
进展为转移是大多数癌症相关死亡的近端原因。然而，关于是什么决定了肿瘤细胞的扩散，还有很多问题有待了解。本文描述了一种新的途径，在乳腺癌，调节上皮间质转化（EMT），运动性和侵袭性。我们确定了两个转录因子，核因子1-C2（NF 1-C2）和叉头框F1（FoxF 1），催乳素/核Janus激活激酶2的下游，对这些过程有相反的影响。我们发现，NF 1-C2在乳腺肿瘤进展过程中丢失，并且几乎总是不存在淋巴结转移。原发性肿瘤中的NF 1-C2水平与更好的患者生存相关。通过表达稳定的版本或使用小干扰RNA来操纵NF 1-C2水平显示NF 1-C2抵消EMT、运动性、侵袭性和肿瘤生长。FoxF 1被发现是NF 1-C2的直接抑制靶点。我们提供了第一个证据FoxF 1在癌症中的作用，并在上皮起源的细胞中调节EMT。FoxF 1的过表达与间充质表型、体外侵袭力增加和裸鼠乳腺癌异种移植物生长增强相关。这些发现的相关性通过乳腺癌细胞分离株中FoxF 1表达和间充质表型之间的相关性得到加强，这与FoxF 1促进侵袭和转移的解释一致。癌症研究; 70（5）; 2020-9。(C)2010年AACR。
Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis. Cancer Res; 70(5); 2020-9. (C) 2010 AACR.