在稳态和癌症中,部分上皮细胞向间充质细胞转化的作用使干性成为可能。
A role for partial epithelial-to-mesenchymal transition in enabling stemness in homeostasis and cancer.
发表日期:2023 Feb 10
作者:
Jeroen Verstappe, Geert Berx
来源:
SEMINARS IN CANCER BIOLOGY
摘要:
干细胞具有自我更新的能力,能够产生分化细胞,从而在稳态和损伤时维持组织。这种结构层次扩展到肿瘤中,这些肿瘤寄宿类似干细胞的细胞,被认为是癌干细胞,它们推广肿瘤并驱动转移和复发。上皮-间充质转化(EMT)过程在发育和癌细胞迁移中发挥重要作用,并表明干性在稳态和癌症中有关联,因此干性可以被获得,并不一定是一种内在的特征。现在,实验证明,激活EMT程序并不一定将细胞推向完全间充质表型,而是推向杂交E/M状态。本文介绍了连接未转化和癌症细胞的EMT状态和干细胞状态的最新进展。最近的文献清楚地表明,杂交EMT状态有更高的概率获得干细胞特征。细胞沿EMT轴的位置与干细胞类似的状态被称为干性窗口。我们展示了细胞的原始EMT状态如何决定EMT/MET诱导程序,以达到干性。最后,我们介绍了干性调节机制和调节反馈环路,以将细胞定位在EMT轴上的某个EMT状态。版权所有©2023年 Elsevier Ltd.出版。
Stem cells have self-renewal capacities and the ability to give rise to differentiated cells thereby sustaining tissues during homeostasis and injury. This structural hierarchy extends to tumours which harbor stem-like cells deemed cancer stem cells that propagate the tumour and drive metastasis and relapse. The process of epithelial-to-mesenchymal transition (EMT), which plays an important role in development and cancer cell migration, was shown to be correlated with stemness in both homeostasis and cancer indicating that stemness can be acquired and is not necessarily an intrinsic trait. Nowadays it is experimentally proven that the activation of an EMT program does not necessarily drive cells towards a fully mesenchymal phenotype but rather to hybrid E/M states. This review offers the latest advances in connecting the EMT status and stem-cell state of both non-transformed and cancer cells. Recent literature clearly shows that hybrid EMT states have a higher probability of acquiring stem cell traits. The position of a cell along the EMT-axis which coincides with a stem cell-like state is known as the stemness window. We show how the original EMT-state of a cell dictates the EMT/MET inducing programmes required to reach stemness. Lastly we present the mechanism of stemness regulation and the regulatory feedback loops which position cells at a certain EMT state along the EMT axis.Copyright © 2023. Published by Elsevier Ltd.