Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells.
Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells.
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Friend白血病病毒整合1是乳腺癌不良预后的预测因子，并促进乳腺癌细胞的转移和癌症干细胞特性
DOI：
10.1002/cam4.1589
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发表时间：
2018-08
期刊：
影响因子：
4
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Yan X;Yu Y;Li L;Chen N;Song W;He H;Dong J;Liu X;Cui J
乳腺癌是世界上最常见的女性癌症；尽管诊断和治疗有了进展，但复发和转移仍然是乳腺癌患者的主要死亡原因。本研究旨在为该病寻找一种有前景的生物标志物。这项研究阐明了(1)Friend白血病病毒整合1(Fli-1)与各种分子亚型的关系，以及(2)Fli-1在乳腺癌中的预后价值。据我们所知，这项研究首次报道了FLI-1是乳腺癌患者预后不良的预测因子，并在三阴性乳腺癌(TNBC)亚型中过度表达。为了进一步验证Fli-1促进TNBC转移的作用，我们进行了一系列的体外功能实验和裸鼠乳房脂肪垫原位移植实验。Fli-1作为一种转录因子，与关键的EMT相关基因(CDH1和VIM)的启动子结合，在转录水平上调节它们的表达，从而诱导上皮-间充质转化(EMT)。Fli-1过表达显著上调间充质标志物的表达。经Fli-1调控后，乳腺干细胞标记物(ALDH1A1和CD133)和乳房形成能力的变化与EMT相关标记物的变化一致。原位异种移植模型进一步证实，沉默Fli-1后干细胞特性的减弱降低了肿瘤形成的能力。这些结果表明，Fli-1是预测乳腺癌患者预后不良的有用指标。此外，对TNBC患者转移机制的初步探讨将为近期乳腺癌的治疗提供一个潜在的靶点。
Breast cancer is the most common cancer in women worldwide; despite the developments in diagnosis and therapy, recurrence and metastasis remain the main causes of death among patients with breast cancer. This study aimed to identify a promising biomarker for this disease. The study clarified (1) the association between Friend leukemia virus integration 1 (FLI‐1) and various molecular subtypes and (2) the prognostic value of FLI‐1 in breast cancer. To the best of our knowledge, this study is the first to report that FLI‐1 is a predictor of poor prognosis in patients with breast cancer and overexpressed in the triple negative breast cancer (TNBC) subtype. To further verify the effect of FLI‐1 in promoting the metastasis of TNBC, we performed a series of functional experiments in vitro and orthotopic xenograft experiments in the mammary fat pad of nude mice. FLI‐1, as a transcription factor, bound to the promoters of key EMT‐related genes (CDH1 and VIM), and regulated their expressions at the transcriptional level, thus induced epithelial‐mesenchymal transition (EMT). The overexpression of FLI‐1 significantly upregulated the expression of mesenchymal markers. After the modulation of FLI‐1, the changes in mammary stem cell markers (ALDH1A1 and CD133) and the capacity to form mammospheres were consistent with those of the EMT‐related markers. The orthotopic xenograft models further confirmed that the attenuation of stem cell traits after silencing FLI‐1 decreased the ability of tumorigenesis. These results indicate that FLI‐1 is a useful predictor of poor prognosis in patients with breast cancer. Furthermore, the preliminary exploration of metastatic mechanism in the patients with TNBC will provide a potential target to treat breast cancer in the near future.
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影响因子：
8
作者：
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通讯作者：
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10.1097/pai.0000000000000227
发表时间：
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影响因子：
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DOI：
10.1002/gcc.22515
发表时间：
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期刊：
Genes, chromosomes & cancer
影响因子：
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作者：
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影响因子：
3.2
作者：
Andreopoulou E;Schweber SJ;Sparano JA;McDaid HM
通讯作者：
McDaid HM