Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers
Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers
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DOI：
10.1073/pnas.0703900104
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发表时间：
2007-06-12
影响因子：
11.1
通讯作者：
Weinberg, Robert A.
中科院分区：
文献类型：
--
作者：
Mani, Sendurai A.;Yang, Jing;Weinberg, Robert A.
上皮性癌细胞从原发肿瘤向远处器官的转移扩散类似于胚胎发育过程中的细胞迁移。利用基因表达谱，我们发现FOXC2转录因子与癌细胞的转移能力有关，FOXC2转录因子在胚胎发育过程中参与决定间充质细胞的命运。FOXC2的表达是小鼠乳腺癌细胞向肺转移能力所必需的，FOXC2的过表达增强了小鼠乳腺癌细胞的转移能力。我们发现FOXC2在经历上皮-间充质转化(EMTs)的细胞中被诱导表达，这些信号包括转化生长因子-SS1和几种EMT诱导的转录因子，如Snail、Twist和Goosecid。FOXC2在EMT过程中特别促进间充质分化，并可能作为协调EMT计划中间充质部分的关键介质。FOXC2的表达与高度侵袭性的基底细胞样乳腺癌亚型显著相关。这些观察表明FOXC2在促进侵袭和转移方面发挥着核心作用，它可能被证明是人类基底细胞样乳腺癌的一个高度特异的分子标志物。
The metastatic spread of epithelial cancer cells from the primary tumor to distant organs mimics the cell migrations that occur during embryogenesis. Using gene expression profiling, we have found that the FOXC2 transcription factor, which is involved in specifying mesenchymal cell fate during embryogenesis, is associated with the metastatic capabilities of cancer cells. FOXC2 expression is required for the ability of murine mammary carcinoma cells to metastasize to the lung, and overexpression of FOXC2 enhances the metastatic ability of mouse mammary carcinoma cells. We show that FOXC2 expression is induced in cells undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of signals, including TGF-ss 1 and several EMT-inducing transcription factors, such as Snail, Twist, and Goosecoid. FOXC2 specifically promotes mesenchymal differentiation during an EMT and may serve as a key mediator to orchestrate the mesenchymal component of the EMT program. Expression of FOXC2 is significantly correlated with the highly aggressive basal-like subtype of human breast cancers. These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers.