乳腺癌肿瘤干细胞在乳腺癌疾病的扩散与进展方面起着关键作用。近期，美德州大学MD安德森癌症中心的科学家认为，对活跃的p53基因为攻击乳腺肿瘤干细胞提供了潜在路径。
长期以来，研究者认为p53基因可控制DNA损伤、缺陷的细胞自我凋亡，并能激活RNA。这能防止分布在器官上的上皮分化细胞，转化为类似于间充质干细胞-受TGF-B(beta)刺激的细胞。
间充质细胞是移动的成体干细胞，能自我繁殖，并分化为各种细胞类型。MD安德森癌症中心分子细胞肿瘤系的教授谈到：防止上皮细胞向间充质细胞转化在癌症转移方面发挥了重要作用。
癌症治疗的希望
我们发现p53激活micro RNA miR-200c，使具有干细胞特性的细胞恢复到上皮细胞的形式。这一方法可对具有干细胞特性的肿瘤起始细胞产生治疗功能。
研究表发大约80%的各类实体瘤开始于上皮细胞。然而，90%的癌症死亡率源于癌症转移并扩散到身体的其他器官。
上皮细胞间质转型（EMT）及其逆向过程在胚胎发展过程中发挥重要作用。研究者将EMT激活与癌症的发展与转移相联系。最近的研究将EMT与在正常和转化细胞中干细胞特性的获取相联系。
细胞状态依赖于p53, miR-200c 水平。
一系列的实验表明p53蛋白质激活miR-200c，产生microRNA，蛋白质和miR-200c的表达上下起伏。
P53基因突变发生在一半以上的肿瘤上，p53基因的失活与癌症相关类型中的糟糕的病症相关。通过miR-200c的重新表达，恢复p53基因突变丧失的功能可能是治疗p53缺陷肿瘤不错的治疗方案。该研究发表于Nature Cell Biology杂志上。（生物谷Bioon.com）
英文链接：http://www.sciencedaily.com/releases/2011/02/110225164707.htm
中文链接：http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=996
生物谷推荐英文摘要
Nature Cell Biology (2011) doi:10.1038/ncb2173
p53 regulates epithelial–mesenchymal transition and stem cell properties through modulating miRNAs
Chun-Ju Chang, Chi-Hong Chao, Weiya Xia, Jer-Yen Yang, Yan Xiong, Chia-Wei Li, Wen-Hsuan Yu, Sumaiyah K. Rehman, Jennifer L. Hsu,Heng-Huan Lee,Mo Liu,Chun-Te Chen,Dihua Yu& Mien-Chie Hung
The epithelial–mesenchymal transition (EMT) has recently been linked to stem cell phenotype1, 2. However, the molecular mechanism underlying EMT and regulation of stemness remains elusive. Here, using genomic approaches, we show that tumour suppressor p53 has a role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of the microRNA miR-200c. p53 transactivates miR-200c through direct binding to the miR-200c promoter. Loss of p53 in mammary epithelial cells leads to decreased expression of miR-200c and activates the EMT programme, accompanied by an increased mammary stem cell population. Re-expressing miR-200c suppresses genes that mediate EMT and stemness properties3, 4 and thereby reverts the mesenchymal and stem-cell-like phenotype caused by loss of p53 to a differentiated epithelial cell phenotype. Furthermore, loss of p53 correlates with a decrease in the level of miR-200c, but an increase in the expression of EMT and stemness markers, and development of a high tumour grade in a cohort of breast tumours. This study elucidates a role for p53 in regulating EMT–MET (mesenchymal–epithelial transition) and stemness or differentiation plasticity, and reveals a potential therapeutic implication to suppress EMT-associated cancer stem cells through activation of the p53–miR-200c pathway.
