Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Cancer Cell. 2014 Oct 13;26(4):534-48. doi: 10.1016/j.ccell.2014.09.002.
Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snail at lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.
蜗牛主要作为一种转录阻遏物，通过抑制黏附蛋白诱导上皮间质转化。新出现的证据表明，蜗牛可以作为一种激活剂；然而，其机制和生物学意义尚不清楚。在这里，我们发现 CREB 结合蛋白 (CBP) 是蜗牛介导的靶基因反式激活的关键因素。CBP 与蜗牛相互作用，并乙酰化蜗牛的赖氨酸 146 和赖氨酸 187，从而阻止抑制复合物的形成。我们进一步鉴定了几个蜗牛激活的靶标，包括 TNF-α，它也是蜗牛乙酰化的上游信号，以及 CCL2 和 CCL5，它们促进肿瘤相关巨噬细胞的募集。在这里，我们介绍了蜗牛诱导靶基因反式激活重塑肿瘤微环境的机制研究结果。
