KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer.
KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer.
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DOI：
10.1038/ncb1974
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发表时间：
2009-11
影响因子：
21.3
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Gumireddy K;Li A;Gimotty PA;Klein-Szanto AJ;Showe LC;Katsaros D;Coukos G;Zhang L;Huang Q
转移是一个复杂的多步骤过程，需要许多基因的协同作用，是癌症死亡的主要原因。调节转移增强和抑制的途径都有助于肿瘤扩散过程。为了鉴定新的转移抑制因子，我们在小鼠模型中建立了正向遗传筛选。我们将全基因组RNAi文库转导到非转移性168 FARN乳腺癌细胞系中，将细胞原位移植到小鼠乳腺脂肪垫中，然后选择可以转移到肺的细胞并鉴定KLF 17基因的RNAi。相反，我们证明了KLF 17在高转移性4 T1乳腺癌细胞系中的异位表达抑制了它们从乳腺脂肪垫转移到肺的能力。我们还表明，抑制KLF 17的表达促进乳腺癌细胞的侵袭和上皮间质转化（EMT），KLF 17的功能直接结合到Id-1的启动子，在乳腺癌中的一个关键的转移调节，以抑制其转录。最后，我们证明，KLF 17的表达显着下调，在原发性人类乳腺癌样本，KLF 17和Id-1的组合表达模式可以作为一个潜在的生物标志物的乳腺癌淋巴结转移。
Metastasis is a complex multi-step process requiring the concerted action of many genes and is the primary cause of cancer deaths. Pathways that regulate metastasis enhancement and suppression both contribute to tumor dissemination process. In order to identify novel metastasis suppressors, we set up a forward genetic screen in a mouse model. We transduced a genome-wide RNAi library into the non-metastatic 168FARN breast cancer cell line, orthotopically transplanted the cells into mouse mammary fat pads, and then selected for cells that could metastasize to the lung and identified an RNAi for the KLF17 gene. Conversely, we demonstrate that ectopic expression of KLF17 in highly metastatic 4T1 breast cancer cell line inhibited their ability to metastasize from the mammary fat pad to the lung. We also show that suppression of KLF17 expression promotes breast cancer cell invasion and epithelial-mesenchymal transition (EMT) and that KLF17 functions by directly binding to the promoter of Id-1, a key metastasis regulator in breast cancer, to inhibit its transcription. Finally, we demonstrate that KLF17 expression is significantly down-regulated in primary human breast cancer samples and that the combined expression patterns of KLF17 and Id-1 can serve as a potential biomarker for lymph node metastasis in breast cancer.
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影响因子：
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