Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal
Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal
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Twist2通过促进上皮-间质转化和癌症干细胞样细胞自我更新促进乳腺癌进展
DOI：
10.1038/onc.2011.181
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发表时间：
2011-11-01
期刊：
影响因子：
8
通讯作者：
Ouyang, G.
中科院分区：
文献类型：
--
作者：
Fang, X.;Cai, Y.;Ouyang, G.
上皮间质转化（EMT）是一个高度保守的细胞程序，在正常胚胎发生和癌症侵袭和转移中具有重要作用。我们在这里报告Twist 2，一种组织特异性碱性螺旋-环-螺旋转录因子，在人类乳腺癌和淋巴结转移中过表达。在乳腺上皮细胞和乳腺癌细胞中，Twist 2的异位过表达导致形态转化、上皮标志物的下调和间充质标志物的上调。此外，Twist 2在体外增强乳腺上皮细胞和乳腺癌细胞的细胞迁移和集落形成能力，并在体内促进肿瘤生长。Twist 2在乳腺上皮细胞和乳腺癌细胞中的异位表达增加了它们的CD 44（高）/CD 24（低）干细胞样细胞亚群的大小和数量，促进了干细胞标志物的表达并增强了干细胞样细胞的自我更新能力。此外，Twist 2的外源性表达导致STAT 3（信号转导子和转录激活子3）的组成性激活和E-钙粘蛋白的下调。因此，Twist 2的过表达可能通过激活EMT程序和增强癌症干细胞样细胞的自我更新而促进乳腺癌的进展。Oncogene（2011）30，4707-4720; doi：10.1038/onc.2011.181; 2011年5月23日在线发表
The epithelial to mesenchymal transition (EMT) is a highly conserved cellular programme that has an important role in normal embryogenesis and in cancer invasion and metastasis. We report here that Twist2, a tissue-specific basic helix-loop-helix transcription factor, is overexpressed in human breast cancers and lymph node metastases. In mammary epithelial cells and breast cancer cells, ectopic overexpression of Twist2 results in morphological transformation, downregulation of epithelial markers and upregulation of mesenchymal markers. Moreover, Twist2 enhances the cell migration and colony-forming abilities of mammary epithelial cells and breast cancer cells in vitro and promotes tumour growth in vivo. Ectopic expression of Twist2 in mammary epithelial cells and breast cancer cells increases the size and number of their CD44(high)/CD24(low) stem-like cell sub-populations, promotes the expression of stem cell markers and enhances the self-renewal capabilities of stem-like cells. In addition, exogenous expression of Twist2 leads to constitutive activation of STAT3 (signal transducer and activator of transcription 3) and downregulation of E-cadherin. Thus, the overexpression of Twist2 may contribute to breast cancer progression by activating the EMT programme and enhancing the self-renewal of cancer stem-like cells. Oncogene (2011) 30, 4707-4720; doi:10.1038/onc.2011.181; published online 23 May 2011