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Spatial and Temporal Relationship between Epithelial–Mesenchymal Transition (EMT) and Stem Cells in Cancer
Clinical Chemistry ( IF 9.3 ) Pub Date : 2024-01-04 , DOI: 10.1093/clinchem/hvad197
Petra den Hollander 1, 2 , Joanna Joyce Maddela 1, 2 , Sendurai A Mani 1, 2
Affiliation  

Background Epithelial–mesenchymal transition (EMT) is often linked with carcinogenesis. However, EMT is also important for embryo development and only reactivates in cancer. Connecting how EMT occurs during embryonic development and in cancer could help us further understand the root mechanisms of cancer diseases. Content There are key regulatory elements that contribute to EMT and the induction and maintenance of stem cell properties during embryogenesis, tissue regeneration, and carcinogenesis. Here, we explore the implications of EMT in the different stages of embryogenesis and tissue development. We especially highlight the necessity of EMT in the mesodermal formation and in neural crest cells. Through EMT, these cells gain epithelial–mesenchymal plasticity (EMP). With this transition, crucial morphological changes occur to progress through the metastatic cascade as well as tissue regeneration after an injury. Stem-like cells, including cancer stem cells, are generated from EMT and during this process upregulate factors necessary for stem cell maintenance. Hence, it is important to understand the key regulators allowing stem cell awakening in cancer, which increases plasticity and promotes treatment resistance, to develop strategies targeting this cell population and improve patient outcomes. Summary EMT involves multifaceted regulation to allow the fluidity needed to facilitate adaptation. This regulatory mechanism, plasticity, involves many cooperating transcription factors. Additionally, posttranslational modifications, such as splicing, activate the correct isoforms for either epithelial or mesenchymal specificity. Moreover, epigenetic regulation also occurs, such as acetylation and methylation. Downstream signaling ultimately results in the EMT which promotes tissue generation/regeneration and cancer progression.

中文翻译:

癌症中上皮-间质转化(EMT)与干细胞之间的时空关系

背景 上皮-间质转化(EMT)通常与癌发生有关。然而,EMT 对于胚胎发育也很重要,并且仅在癌症中重新激活。将胚胎发育过程中的 EMT 发生过程与癌症中的 EMT 联系起来可以帮助我们进一步了解癌症疾病的根本机制。内容 在胚胎发生、组织再生和癌变过程中,有一些关键的调控元件有助于 EMT 以及干细胞特性的诱导和维持。在这里,我们探讨 EMT 在胚胎发生和组织发育不同阶段的影响。我们特别强调 EMT 在中胚层形成和神经嵴细胞中的必要性。通过 EMT,这些细胞获得上皮间质可塑性 (EMP)。随着这种转变,关键的形态变化发生并通过转移级联以及损伤后的组织再生进行。干细胞样细胞,包括癌症干细胞,是由 EMT 产生的,在此过程中上调干细胞维持所需的因子。因此,了解癌症中干细胞觉醒的关键调节因子非常重要,这会增加可塑性并促进治疗抵抗,从而制定针对该细胞群的策略并改善患者的治疗效果。总结 EMT 涉及多方面的监管,以实现促进适应所需的流动性。这种调节机制,即可塑性,涉及许多协作的转录因子。此外,翻译后修饰(例如剪接)可激活上皮或间质特异性的正确亚型。此外,还发生表观遗传调控,例如乙酰化和甲基化。下游信号传导最终导致 EMT,从而促进组织生成/再生和癌症进展。
更新日期:2024-01-04
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