EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression.
EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression.
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EMT和Stemness：通过在发育和癌症进展方面的替代剪接调整的灵活过程。
DOI：
10.1186/s12943-016-0579-2
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发表时间：
2017-01-30
期刊：
影响因子：
37.3
通讯作者：
Ghigna C
中科院分区：
文献类型：
--
作者：
Pradella D;Naro C;Sette C;Ghigna C
上皮-间质转化（EMT）与转移形成以及癌症干细胞的产生和维持相关。因此，EMT促进了肿瘤的侵袭、异质性和化疗耐药性。这些过程中涉及的形态和功能变化需要基因表达的强大重编程，这在转录水平上仅部分完成。选择性剪接是基因表达调控的另一个重要层面，它扩展了细胞蛋白质组。基因表达的转录后调节中的这一步骤严格控制上皮和间充质状态之间以及干细胞分化期间的细胞身份。重要的是，剪接因子功能和癌症特异性剪接异构体表达的失调经常发生在人类肿瘤中，这表明选择性剪接调节对癌症生物学的重要性。在这篇综述中，我们简要地讨论了EMT计划在发展，干细胞分化和癌症进展中的作用。接下来，我们集中在选定的例子中的关键因素参与EMT和干细胞分化，通过选择性剪接机制转录后调节。最后，我们描述了直接协调癌症干细胞生物学和肿瘤EMT的相关致癌剪接变体，这可能被设想为治疗干预的新靶点。
Epithelial-to-mesenchymal transition (EMT) is associated with metastasis formation as well as with generation and maintenance of cancer stem cells. In this way, EMT contributes to tumor invasion, heterogeneity and chemoresistance. Morphological and functional changes involved in these processes require robust reprogramming of gene expression, which is only partially accomplished at the transcriptional level. Alternative splicing is another essential layer of gene expression regulation that expands the cell proteome. This step in post-transcriptional regulation of gene expression tightly controls cell identity between epithelial and mesenchymal states and during stem cell differentiation. Importantly, dysregulation of splicing factor function and cancer-specific splicing isoform expression frequently occurs in human tumors, suggesting the importance of alternative splicing regulation for cancer biology. In this review, we briefly discuss the role of EMT programs in development, stem cell differentiation and cancer progression. Next, we focus on selected examples of key factors involved in EMT and stem cell differentiation that are regulated post-transcriptionally through alternative splicing mechanisms. Lastly, we describe relevant oncogenic splice-variants that directly orchestrate cancer stem cell biology and tumor EMT, which may be envisioned as novel targets for therapeutic intervention.