A molecular portrait of epithelial-mesenchymal plasticity in prostate cancer associated with clinical outcome.
A molecular portrait of epithelial-mesenchymal plasticity in prostate cancer associated with clinical outcome.
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DOI：
10.1038/s41388-018-0488-5
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发表时间：
2019-03
期刊：
影响因子：
8
通讯作者：
Hollier BG
中科院分区：
文献类型：
--
作者：
Stylianou N;Lehman ML;Wang C;Fard AT;Rockstroh A;Fazli L;Jovanovic L;Ward M;Sadowski MC;Kashyap AS;Buttyan R;Gleave ME;Westbrook TF;Williams ED;Gunter JH;Nelson CC;Hollier BG
癌细胞通过上皮-间质转化（epithelial - mesenchymal transition， EMT）程序在上皮和间质表型状态之间转换的倾向可以调节转移过程、癌症进展和治疗耐药性。利用可逆EMT模型的转录研究显示，转移性去势抵抗性前列腺癌（mCRPC）的临床样本中，间充质-上皮恢复转化（MErT）富集。从这种富集中，发现了一种转移源基因标记，预测了多种人类癌症类型的更快的癌症复发和降低的生存期。此外，MErT的转录谱并不是EMT的简单镜像，因为肿瘤细胞在可逆EMT后保留了转录“记忆”。这种记忆在mCRPC样品中也得到了丰富。总之，我们的研究揭示了上皮-间质可塑性的转录谱，并强调了MErT独特的转录特性。此外，我们的研究结果提供了证据，支持上皮可塑性与多种人类癌症类型的不良临床结果之间的关联。
The propensity of cancer cells to transition between epithelial and mesenchymal phenotypic states via the epithelial–mesenchymal transition (EMT) program can regulate metastatic processes, cancer progression, and treatment resistance. Transcriptional investigations using reversible models of EMT, revealed the mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical samples of metastatic castrate resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified that predicted more rapid cancer relapse and reduced survival across multiple human carcinoma types. Additionally, the transcriptional profile of MErT is not a simple mirror image of EMT as tumour cells retain a transcriptional “memory” following a reversible EMT. This memory was also enriched in mCRPC samples. Cumulatively, our studies reveal the transcriptional profile of epithelial–mesenchymal plasticity and highlight the unique transcriptional properties of MErT. Furthermore, our findings provide evidence to support the association of epithelial plasticity with poor clinical outcomes in multiple human carcinoma types.
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影响因子：
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
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