TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer.
TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer.
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DOI：
10.1158/0008-5472.can-15-2322
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发表时间：
2016-09-01
期刊：
影响因子：
11.2
通讯作者：
Alarcón CR
中科院分区：
文献类型：
--
作者：
Lee H;Goodarzi H;Tavazoie SF;Alarcón CR
发育转录因子 SOX4 有助于多种实体癌类型的转移扩散，但其介导癌症进展的直接靶基因尚不清楚。使用系统的分子和基因组方法，我们确定 TMEM2 跨膜蛋白基因是 SOX4 的直接转录靶标。 TMEM2 在乳腺癌细胞中被 SOX4 转录激活，与 SOX4 一样，TMEM2 被发现可介导促侵袭和促迁移效应。同样，TMEM2 足以促进乳腺癌细胞的转移性定植，并且其在原发性乳腺肿瘤中的表达与转移性复发的可能性较高相关。鉴于早期证据表明 SOX4 或 TMEM2 的基因失活会在心脏发育中产生类似的缺陷，我们的研究结果使我们提出，TMEM2 可能不仅介导 SOX4 对癌症进展的病理作用，而且还可能介导其对胚胎发育的贡献。
The developmental transcription factor SOX4 contributes to the metastatic spread of multiple solid cancer types, but its direct target genes that mediate cancer progression are not well defined. Using a systematic molecular and genomic approach, we identified the TMEM2 transmembrane protein gene as a direct transcriptional target of SOX4. TMEM2 was transcriptionally activated by SOX4 in breast cancer cells where, like SOX4, TMEM2 was found to mediate pro-invasive and pro-migratory effects. Similarly, TMEM2 was sufficient to promote metastatic colonization of breast cancer cells and its expression in primary breast tumors associated with a higher likelihood of metastatic relapse. Given earlier evidence that genetic inactivation of SOX4 or TMEM2 yield similar defects in cardiac developmental, our findings lead us to propose that TMEM2 may not only mediate the pathologic effects of SOX4 on cancer progression but also potentially its contributions to embryonic development.