Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.
Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.
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DOI：
10.1371/journal.pone.0012445
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发表时间：
2010-08-27
期刊：
影响因子：
3.7
通讯作者：
Sarkar FH
中科院分区：
文献类型：
--
作者：
Kong D;Banerjee S;Ahmad A;Li Y;Wang Z;Sethi S;Sarkar FH
目前诊断为前列腺癌（PCa）的患者的管理是非常有效的;然而，去势抵抗性前列腺癌（CRPC）的肿瘤复发和随后的转移导致生存结局不佳，这表明迫切需要对肿瘤复发的新机制的理解，这对于设计新的治疗方法至关重要。前列腺癌的复发和转移与前列腺癌干细胞或癌症起始细胞的生物学密切相关，这使人联想到上皮向间质转化（EMT）表型的获得。越来越多的证据表明，EMT型细胞与癌症干细胞样细胞共享许多生物学特征。在本研究中，我们发现具有EMT表型的PCa细胞表现出干细胞样细胞特征，其特征在于Sox 2、Nanog、Oct 4、Lin 28 B和/或Notch 1的表达增加，与小鼠的克隆形成和球体（prostasphere）形成能力和致瘤性增强一致，这与miR-200和/或let-7家族的表达降低相关。通过重新表达miR-200抑制EMT型细胞的前列腺球形成能力，并降低Notch 1和Lin 28 B的表达。Lin 28 B的下调增加了let-7的表达，这与被抑制的自我更新能力一致。这些结果表明，miR-200在将癌干细胞样细胞的特征与PCa中的EMT样细胞特征联系起来方面发挥了关键作用。通过使用新型试剂将EMT表型逆转为间质-上皮转化（MET）表型来选择性消除癌症干细胞样细胞将可用于预防肿瘤复发，特别是通过消除作为肿瘤发展和复发的“根本原因”的那些细胞。
Current management of patients diagnosed with prostate cancer (PCa) is very effective; however, tumor recurrence with Castrate Resistant Prostate Cancer (CRPC) and subsequent metastasis lead to poor survival outcome, suggesting that there is a dire need for novel mechanistic understanding of tumor recurrence, which would be critical for designing novel therapies. The recurrence and the metastasis of PCa are tightly linked with the biology of prostate cancer stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT) phenotype. Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. In this study, we found that PCa cells with EMT phenotype displayed stem-like cell features characterized by increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with enhanced clonogenic and sphere (prostasphere)-forming ability and tumorigenecity in mice, which was associated with decreased expression of miR-200 and/or let-7 family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere-forming ability of EMT-type cells and reduced the expression of Notch1 and Lin28B. Down-regulation of Lin28B increased let-7 expression, which was consistent with repressed self-renewal capability. These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET) phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the “Root Cause” of tumor development and recurrence.
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影响因子：
5.2
作者：
Kong, Dejuan;Li, Yiwei;Wang, Zhiwei;Banerjee, Sanjeev;Ahmad, Aamir;Kim, Hyeong-Reh Choi;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
11.2
作者：
Gu, Guangyu;Yuan, Jialing;Kasper, Susan
通讯作者：
Kasper, Susan
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
DOI：
10.1016/j.bbadis.2009.02.012
发表时间：
2009-04-01
影响因子：
6.2
作者：
Marian, Calin O.;Shay, Jerry W.
通讯作者：
Shay, Jerry W.
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA