Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Cell Cycle. 2011 Sep 1;10(17):2865-73. doi: 10.4161/cc.10.17.17188.
Epithelial-mesenchymal transition (EMT) is an essential developmental program that becomes reactivated in adult tissues to promote the progression of cancer. EMT has been largely studied by examining the beginning epithelial state or the ending mesenchymal state without studying the intermediate stages. Recent studies using trophoblast stem (TS) cells paused in EMT have defined the molecular and epigenetic mechanisms responsible for modulating the intermediate "metastable" stages of EMT. Targeted inactivation of MAP3K4, knockdown of CBP, or overexpression of SNAI1 in TS cells induced similar metastable phenotypes. These TS cells exhibited epigenetic changes in the histone acetylation landscape that cause loss of epithelial maintenance while preserving self-renewal and multipotency. A similar phenotype was found in claudin-low breast cancer cells with properties of EMT and stemness. This intersection between EMT and stemness in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness of developmental EMT systems to understand EMT in cancer.
上皮-间充质转化 (EMT) 是一种重要的发育程序，在成人组织中重新激活以促进癌症的进展。EMT 主要通过研究起始上皮状态或结束间充质状态来研究，而没有研究中间阶段。最近使用处于 EMT 暂停状态的滋养层干细胞 (TS) 细胞的研究定义了负责调节 EMT 中间“亚稳态”阶段的分子和表观遗传机制。在 TS 细胞中靶向失活 MAP3K4、敲低 CBP 或过表达 SNAI1 诱导了类似的亚稳态表型。这些 TS 细胞表现出组蛋白乙酰化景观中的表观遗传变化，导致上皮维持丧失，同时保留自我更新和多能性。具有 EMT 和干性特征的 Claudin-low 乳腺癌细胞中也发现了类似的表型。TS 细胞和 Claudin-low 转移性乳腺癌中 EMT 和干性之间的这种交集表明，发育 EMT 系统在理解癌症中的 EMT 方面具有实用性。
